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The floriculture industry is experiencing rapid growth, expanding annually at 10-15%. Tuberose (Polianthes tuberosa Linn.), a perennial bulbous flowering plant from the Asparagaceae family, holds significant economic value due to its use in cut flowers, garlands, and the extraction of high-value essential oils. Despite its commercial importance, tuberose faces challenges in genetic improvement due to limited genetic variability, self-incompatibility, and seed sterility. Traditional breeding methods are thus constrained. Mutation breeding, utilizing ionizing radiation and chemical mutagens such as Ethyl-methanesulphonate (EMS), offers a potential solution by inducing genetic variability. This study investigates the effects of gamma rays and EMS on tuberose variety Single Mexican to enhance its growth and floral characteristics. Twelve bulbs per treatment were exposed to varying doses of EMS (0.25%, 0.5%, 0.75%, 1%) and gamma rays (5 Gy, 10 Gy, 15 Gy, 20 Gy), with controls for each mutagen. The bulbs were grown in a Randomized Block Design over two growing seasons (2022-2023, 2023-2024) at the Horticulture Research Centre, Sardar Vallabhbhai Patel University of Agriculture and Technology, Meerut, India. Parameters such as days to bulb sprouting, survival percentage at 30 days, plant height at 60 days, leaf number, leaf length, days to first flower, spike number and length, rachis length, floret number, diameter, and weight were recorded. Results showed that lower doses of gamma rays (5 Gy) and EMS (0.25%) significantly improved these traits, while higher doses had adverse effects. These findings suggest that controlled application of lower doses of gamma rays and EMS can effectively enhance the growth and ornamental quality of tuberose, offering a valuable approach for its genetic improvement in floriculture. [ABSTRACT FROM AUTHOR]

Citrus, one of the most popular fruit crops grown worldwide, has high nutritional, medicinal and commercial value. This experiment aimed to investigate the effects of gamma radiation with various doses, including 0 Gy, 5Gy, 10 Gy, 15 Gy, 20 Gy, 25Gy, 30 Gy, 35 Gy, 40 Gy and 45 Gy of cobalt 60 sources on acid lime variety Agamalai citrus, (Citrus aurantifolia). The study was carried out at the Horticulture College and Research Institute in Periyakulam. The mutagenic efficiency and effectiveness were evaluated using the frequency of chlorophyll mutations and the biological damage in M1 plants. The stomatal index reduces (19.62 %-13.99%) with increasing treatment dose, compared to control (20.39%), although guard cell dimensions, such as length (6.09 µm) in 15 Gy and breadth (4.56 µm) in 5 Gy increase with higher dose treatment than untreated (3.71 µm, 3.54 µm). Identifying the mutagenic efficiency and effectiveness of the mutagen and maximising the lethal dosage is the first stage in any mutagenesis research. This work will serve as a foundation for subsequent gamma-irradiation studies in acidlime to generate desirable mutants. [ABSTRACT FROM AUTHOR]

Induction of polyploidy can be achieved using chemical mutagen or antimitotic compounds that affect cell division, resulting in doubling number of chromosomes. A new inducer for chromosome doubling mutation agent-bio-catharantin-may be used. This report determined the mortality rate of bio-catharantin used for mutation induction experiments in shallot plants. Two sets of experiments were arranged in a two factorial randomized block design, i.e. five levels of biocatharantin concentration treatment (0.0, 2.5, 5.0, 10.0, and 15.0%) combined with soaking periods of 6-, 12-, and 24-h. Each combination was repeated three times, with five seed bulbs in each combination. The result shows that the mortality rate of shallot tends to increase with increasing concentration and soaking time. A high percentage of the mortality rate was found at all concentrations other than control at 24-h soaking time. Hence, the mortality rate of prolonged soaking (24 h) is greater at higher concentrations. However, at lower concentrations of 2.5 and 5% for 6- and 12-h soaking time the mortality rate was low (13 and 27%, 7 and 60%, respectively). Meanwhile, at 10%, the result shows relatively high mortality rates (13 and 73%, respectively). Administration of bio-catharantin at 5 and 10% with a 12-h soaking period causes optimal mortality rate, whereas the germination rate shows the opposite trend. To find the accuracy of the efficacy of bio-catharantin concentration between 5-10%, we introduced 7.5% in the second experiment. The concentration of 7.5% has a significant effect on leaf diameter, where it becomes smaller as inhibited by increased concentration (2.5 and 5.0%) but becomes larger again at 7.5% (0.59 mm) nearing control (0.70 mm) and drops again to 0.23 mm (10%). This is not usually the trend of inhibition when a larger concentration is used except when polyploidization has taken effect, presumably at 7.5% bio-catharantin with a 12-h immersion period. [ABSTRACT FROM AUTHOR]

This study was conducted at Bangladesh Institute of Nuclear Agriculture (BINA) research farm, Mymensingh during November 2021 to March 2022 to evaluate the effect of gamma irradiation and chemical mutagen on growth and yield of onion. The experiment was laid out in randomized complete block design with three replicates and nine (9) treatments viz. four gamma irradiation doses (GD50, GD100, GD150, GD200) and four Ethyl Methane Sulphonate (EMS) doses (ED0.1%, ED0.3%, ED0.5%, ED0.7%) and control. The results showed that almost all the parameter studied were significantly influenced by the treatments. The highest germination 90.16%, survivability 94.33%, SCMR value 63.56μmol/ms, Total Soluble Solids (TSS) 15.10 %Brix were recorded in T1(GD50) treatment and the maximum mortality 67% in T7(ED0.5%), shoot length 17.18 cm in T5(ED0.1%), root length (3.35 cm) in T5(0.1%), neck diameter 1.06cm in T8 (ED0.7%), bulb diameter 5.36 in T4(GD200), plant height 70 cm in T4(GD200), single bulb weight 75g in T4(GD200) and fresh yield 24t/ha in T5(ED0.1%,). The minimum germination 8.33% in T3(GD150), survivability 36.66% in T8(ED0.07%), mortality 5.66% in T1 (GD50), shoot length 8.26cm in T3(GD150), root length 0.9 cm in T4 , SCMR value 55.26 μmol/ms in T2 (GD100 ), plant height 51cm in T3(GD150), bulb diameter 3.91 cm in T7(ED0.5) , neck diameter 0.84cm in T6 , single bulb weight 42g in T7 (ED0.5 ), fresh yield 1.5t/ha in T3(GD150 ), TSS 10.40 %Brix in T7 (ED0.5%) were observed. Gamma irradiation GD200 (T4) and EMS 0.1% (T5) performed superior considering growth and yield of onion.

Sustainable wheat production and higher genetic gains can be realized by broadening the genetic base and improving the well adapted varieties. In the present study, a multi-year experiment involving induced mutagenesis was conducted to create genetic variation, assess trait associations and genetic divergence in four wheat varieties with differential grain texture treated with six doses of gamma rays and ethyl methane sulfonate using ten agro-morphological traits. Healthy selfed seeds of four bread wheat varieties with differential texture were irradiated using six doses ranging from 175 Gy-300 Gy of gamma rays (Co60: BARC, Mumbai) and six concentrations of ethyl methanesulfonate (0.3–1.3%) (Sigma-Aldrich, Bangalore, India) to evaluate variability, character association and degree of genetic diversity induced among the mutagenic treatments of wheat varieties with differential grain texture. Significant inter-population differences were observed for almost all the traits. The sample mean of twelve mutant populations in each of the cultivar exhibited superior quantitative phenotypic traits and increased values of the genetic parameters. Based on association and variability studies, plant height, spike length, grain filling period, biological yield per plant and harvest index can be used as early generation criteria for maximum genetic improvement. Multivariate studies indicated the contribution of various traits towards divergence and indicated the efficiency of mutagens in generating variability. Gamma-irradiation dosages between 200–250 Gy and 0.5–1.1% EMS for soft-textured varieties, whereas doses between 225–275 Gy and 0.5–0.9% EMS were found to be most potent for semi-hard-textured varieties. Assessment of mutagen sensitivity showed that semi-hard wheat varieties were responsive to both mutagens, particularly EMS and generated higher variability and divergence than the soft textured varieties. Hence, gamma rays were proved to be more effective in generating higher variability than ethyl methanesulfonate. A total of 117 putative mutants were identified with desirable agro-morphological attributes. Among these, mutants with higher inter-cluster distance can be used as parents in hybridization programs and serve as important genetic resources in future wheat improvement programs. [ABSTRACT FROM AUTHOR]

The analysis of cytological abnormalities is an important method for identifying the potential of a chemical as a mutagen for future heritable genetic changes, the level of genotype-mutagen interaction and site-specific activity for the nature and/or different concentrations of the mutagen. The research aims to determine the limits of the variability of genotypes of different origins, especially those with wide ecological and genetic variability, and to show the interaction between the variety and the mutagen. Winter wheat grains of several varieties (Balaton, Borovytsia, Zelenyi Hai, Zoloto Ukrainy, Kalancha, Niva Odeska, Polianka, Pochayna) were treated with dimethyl sulphate at concentrations of 0.0125%, 0.025%, 0.05%, and exposure was 24 hours. The cytogenetic activity was studied by the frequency and spectrum of chromosomal rearrangements in the corresponding phases of cell division, depending on the variety and concentration of the mutagen as the main factors affecting these parameters, as well as the main features of the spectrum, such as the overall rate of chromosomal rearrangements, the number of fragments and double fragments, bridges, micronuclei, and lagging chromosomes. The studied concentrations of the supermutagen were found to have a significant effect on all analysed parameters and can be classified as optimal and high concentration levels in terms of the effect on cytological activity and mitotic problems for the factor, despite previous studies. The variety factor has a much greater impact on the nature and frequency of certain types of aberrations than an increase in the mutagen concentration, it was characterised by a much greater site-specific effect than other chemical agents, and various variants in mutagenic effects were identified according to the subject’s genotype. It was generalised that the features that reproduced the effect of the mutagen, according to the discriminant analysis, were the total frequency, the frequency of fragments and double fragments, and bridges. In practical use in the genetic improvement of plants and for obtaining valuable traits, the optimal concentrations are 0.0125%, and 0.025%, which is planned to be further confirmed on a wider range of genotypes and by mutation studies for the next (second or third) generations

The North-western Himalayan region requires unique varietal traits for the cultivation and quality of grain produced. Wheat varieties released for this zone in the past remained very popular among the farmers. However, with the passage of time certain traits such as the appearance of pathogenic rust races and grain softness have become threat to the fecundity of these genotypes and needs immediate improvement in this region. Mutation breeding facilitates improving one or two traits of a popular cultivar and to generate variability for most of plant traits upon which selection can be imposed. The purpose of this study is to evaluate the mutagenic sensitivity, effectiveness and efficiency of physical and chemical mutagens in four bread wheat varieties with differential grain texture. Four bread wheat varieties; HS 490, HPW 89, HPW 360 and HPW 251 were irradiated using six doses of gamma rays (γ-rays) ranging from 175 to 300 Gy; Co60 source (BARC, Mumbai, India) and six doses of ethyl methane sulfonate (EMS) ranging from 0.3 to 1.3%; EMS (Sigma-Aldrich, Bangalore, India) to assess their mutation sensitivity, effectiveness, efficiency and spectrum of induced macro-mutations in M1 and M2 generation. Based on mutagen sensitivity tests, both gamma rays and ethyl methane sulfonate had similar effects as the doses/concentrations increased in all four varieties. Ethyl methane sulfonate had a discernible effect on seed germination and growth parameters as compared to gamma irradiated treatments. Pollens viability studies confirmed the differential effects of both mutagens on germination and plant survivability. The LD50 and LC50 values varied between 290–315 Gy for gamma rays and 0.90–1.35% for EMS under controlled laboratory conditions, however, the range substantially differs for gamma rays (240–290 Gy) and for EMS (0.50–1.1%) under field conditions, irrespective of the variety treated. The frequency of chlorophyll mutations was low and showed a linear correlation with the doses/concentrations of the mutagen. A total of 117 putative mutants with desirable agro-morphological characteristics were also isolated. Mutagenic effectiveness and efficiency results showed that gamma irradiation doses of 250–300 Gy and ethyl methane sulfonate of 0.7–1.3% were most potent for an effective mutation breeding programme in wheat crop. It was found that semi-hard textured varieties showed higher sensitivity to chemical mutagens as compared to soft-textured varieties. Gamma irradiation dose of 250–300 Gy and ethyl methane sulfonate concentration of 0.7–1.3% were found to be most effective and efficient across four bread wheat varieties and can be used in large scale mutagenesis programmes. [ABSTRACT FROM AUTHOR]

Mycoplasmas, autonomously culturable bacteria with the smallest genome, are an important organism to understand the minimal form of life. Mutagenesis using mutagens is a useful methodology for understanding the essential regions of genomic information. Ultraviolet light (UV) and trimethyl psoralen (TMP) are mutagens known to induce various mutations; the latter is reported to specifically induce deletions in nematodes. However, their mutagenic effects on mycoplasma are not known. Here, we exposed Metamycoplasma salivarium to UV-C light or TMP and UV-A as mutagens, and analyzed the mutational pattern after serial cultivation ranging from 34 to 56 rounds for different lineages. Our results showed that more deletions, but fewer point mutations, were induced with TMP and UV-A than with UV-C, indicating the usefulness of TMP in inducing deletions. In addition, we compared our results with mutational data from other studies, which suggested that the combination of TMP and UV-A or UV-C exposure both induced point mutations that were highly biased toward C-T and G-A transitions. These data provide useful basic knowledge for mutational studies on M. salivarium. [ABSTRACT FROM AUTHOR]

This study was conducted at Bangladesh Institute of Nuclear Agriculture (BINA) research farm, Mymensingh during November 2021 to March 2022 to evaluate the effect of gamma irradiation and chemical mutagen on growth and yield of onion. The experiment was laid out in randomized complete block design with three replicates and nine (9) treatments viz. four gamma irradiation doses (GD50, GD100, GD150, GD200) and four Ethyl Methane Sulphonate (EMS) doses (ED0.1%, ED0.3%, ED0.5%, ED0.7%) and control. The results showed that almost all the parameter studied were significantly influenced by the treatments. The highest germination 90.16%, survivability 94.33%, SCMR value 63.56µmol/ms, Total Soluble Solids (TSS) 15.10 %Brix were recorded in T1(GD50) treatment and the maximum mortality 67% in T7(ED0.5%), shoot length 17.18 cm in T5(ED0.1%), root length (3.35 cm) in T5(0.1%), neck diameter 1.06cm in T8 (ED0.7%), bulb diameter 5.36 in T4(GD200), plant height 70 cm in T4(GD200), single bulb weight 75g in T4(GD200) and fresh yield 24t/ha in T5(ED0.1%,). The minimum germination 8.33% in T3(GD150), survivability 36.66% in T8(ED0.07%), mortality 5.66% in T1 (GD50), shoot length 8.26cm in T3(GD150), root length 0.9 cm in T4, SCMR value 55.26 µmol/ms in T2 (GD100 ), plant height 51cm in T3(GD150), bulb diameter 3.91 cm in T7(ED0.5), neck diameter 0.84cm in T6, single bulb weight 42g in T7 (ED0.5 ), fresh yield 1.5t/ha in T3(GD150 ), TSS 10.40 %Brix in T7 (ED0.5%) were observed. Gamma irradiation GD200 (T4) and EMS 0.1% (T5) performed superior considering growth and yield of onion. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) is a fruit caryopsis, well known for its high calorific value and presence of high antioxidant phytochemicals such as flavonoids and anthocyanins. Further exposure of crops to different doses of physical mutagens is useful to give insight into development of quality traits for plant breeding. So, the objective of the present study was to analyse the effects of gamma irradiation on black rice seeds that were exposed to different radiation doses and to evaluate the irradiation effect on physiological and biochemical characteristics of plants. Variations were observed among different doses from non-enzymatic antioxidant activities that showed the increasing flavonoids, phenolics and carotenoids accumulation from low to high doses. A high dose irradiation releases, high amount of H2O2 as compare to O2- indicating the involvement of enzymatic antioxidants as a defence mechanism. An inverse relation was shown between peroxidase and catalase enzyme and concentration of Superoxide dismutase also increased with increasing doses. To know the level of stress on cellular metabolism, total proline and malon dialdehyde accumulation was estimated and both showed positive results for increasing doses. In case of measurement of photosynthetic parameters, chlorophyll concentration increased from 50 Gy to 100 Gy and decreased from 150 Gy to 200 Gy due to peroxidation of membrane. Significant effect was not observed in the concentration of soluble sugar among various doses. Thus, the present study, was useful to isolating effective dose (50Gy, 100 Gy) that may contribute towards advancement of qualitative traits for future breeding purposes. [ABSTRACT FROM AUTHOR]

In this study, the mutagenic effects of different doses and exposure times of oryzalin and Nitrogen Protoxide (N2O) were tested for stimulating polyploid on 41 B and Fercal grapevine rootstocks seedlings. Ploidy changes were examined by morphological, cytological, macroscopic, and microscopic methods. Leaf thickness, chlorophyll contents, stomatal sizes, and chloroplast numbers of polyploid seedlings stimulated with mutagens increased but their stomatal densities decreased. Flow cytometry (FC) analyses were performed on 50 samples selected by morphological and microscopic preliminary determinations. In FC analyses, 1 tetraploid seedling and 4 mixoploid seedlings from Fercal offspring and 1 mixoploid seedling from 41 B offspring were verified. The nuclear DNA content of tetraploid and mixoploid seedlings were increased by 2.00 and 1.34-fold, respectively, when compared to their diploid parents. Chromosome counts in root tip samples propagated in vitro from the tetraploid Fercal offspring confirmed a 2-fold increase compared to the diploid parent. In polyploidy induction studies, it was deemed appropriate to use FC analysis and chromosome count together to confirm the ploidy levels of mutants. Oryzalin and N2O applications at different doses and exposure times were found to be effective for inducing polyploidy in 41 B and Fercal grapevine rootstocks. [ABSTRACT FROM AUTHOR]

The use of mutagens in plant breeding is used to create new germplasm, increase agricultural yield, quality, and resistance to diseases and pests. Mutagens are physical or chemical factors that can alter the DNA or RNA structure of an organism, causing mutations above the expected level. One of the most common and potent chemical mutagens is EMS (ethyl-methane sulfonate), which produces point mutations in plants, but to a lesser degree can also cause the loss or deletion of a chromosomal region. This study used inter-primer binding site (iPBS) and coupled restriction enzyme digestion inter-primer binding site (CRED-iPBS) technique analysis to determine the effect of EMS mutagens on methylation rates in wheat genotypes at seedling growth stage. Treatments with five different EMS concentrations (0%; control, 0.1%, 0.2%, 0.3%, and 0.4%) at four different times (0; control, 3, 6, and 9 h) were used. Inter-primer binding site (iPBS) markers were employed to assess genomic instability and cytosine methylation in treated wheat. In seeds treated with EMS at different concentrations and times, the disappearance of regular bands and the formation of new bands due to the effects of the EMS mutagen revealed that genetic diversity exists. The CRED-iPBS analysis revealed that the 3 h + 0.1% EMS treatment produced the highest MspI polymorphism value (19.60%), while the 9 h + 0.1% EMS treatment produced the lowest value (10.90%). The mutagenic effects of EMS treatments had considerable polymorphism on a variety of impacts on the cytosine methylation and genomic instability of wheat. According to the current research, EMS mutagenesis may be a practical method for accelerating breeding programs to produce enough genetic diversity in wheat populations. Mutation-assisted breeding and the subsequent selection of desirable mutants using genetic markers may also be carried out in wheat utilizing an integrated strategy. [ABSTRACT FROM AUTHOR]

The purpose of our study was to show the possibilities of a chemical supermutagen in the regular induction of certain types of mutations. Winter wheat dry seeds of eight varieties were acted with water (control) and DAB (1.4-bisdiazoacetylbutane) action in concentrations of 0.1%, 0.1%, 0.3%. Studies have shown that the use of this mutagen is expedient from the point of view of obtaining valuable forms of low-growing, earlyripening, late-ripening, high-yielding lines, forms with high productive tillering. The mutagen by its nature has a rather low affinity, at least for this group of genotypes, however, this factor still affects the frequency of some types of mutations. Even extreme concentrations of this mutagenic agent did not lead to a significant decrease in the number of mutations; however, they reached a maximum in the spectrum of possible changes. Further studies are needed on changes in photosynthetic activity and associated persistence. [ABSTRACT FROM AUTHOR]

Wheat, which is scientifically known as Triticum aestivum L., is a very nutritious grain that serves as a key component of the human diet. The use of mutation breeding as a tool for crop improvement is a reasonably rapid procedure, and it generates a variety that may be used in selective breeding programs as well as functional gene investigations. The present experiment was used to evaluate the potential application of a conventional chemical mutagenesis technique via sodium azide (NaN3) for the germination and seedling growth stage in wheat. Experiments with NaN3 mutagenesis were conducted using four different treatment periods (0, 1, 2, and 3 h) and five different concentrations (0, 0.5, 1, 1.5, and 2 mM). The genomic instability and cytosine methylation of wheat using its seeds were investigated after they were treated. In order to evaluate the genomic instability and cytosine methylation in wheat that had been treated, interprimer binding site (iPBS) markers were used. The mutagenic effects of NaN3 treatments had considerable polymorphism on a variety of impacts on the cytosine methylation and genomic instability of wheat plants. The results of the experiment showed considerable changes in the iPBS profiles produced by the administration of the same treatments at different dosages and at different times. Coupled restriction enzyme digestion interprimer binding site (CRED-iPBS) assays identified changes in gDNA cytosine methylation. The highest polymorphism value was obtained during 1 h + 2 mM NaN3, while the lowest (20.7%) was obtained during 1 h + 1.5 mM NaN3. Results showed that treatments with NaN3 had an effect on the level of cytosine methylation and the stability of the genomic template in wheat plants in the germination stage. Additionally, an integrated method can be used to for mutation-assisted breeding using a molecular marker system in wheat followed by the selection of desired mutants. [ABSTRACT FROM AUTHOR]

IntroductionThe antiviral activity of different mutagens against single-stranded RNA viruses is well documented; however, their activity on the replication of double-stranded RNA viruses remains unexplored. This study aims to investigate the effect of different antivirals on the replication of a chicken embryo fibroblast-adapted Infectious Bursal Disease virus, FVSKG2. This study further explores the antiviral mechanism utilized by the most effective anti-IBDV agent.MethodsThe cytotoxicity and anti-FVSKG2 activity of different antiviral agents (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated. The virus was serially passaged in chicken embryo fibroblasts 11 times at sub-cytotoxic concentrations of ribavirin, 5-fluorouracil or amiloride. Further, the possible mutagenic and non-mutagenic mechanisms utilized by the most effective anti-FVSKG2 agent were explored.Results and DiscussionRibavirin was the least cytotoxic on chicken embryo fibroblasts, followed by 5-fluorouracil, amiloride and 5-azacytidine. Ribavirin inhibited the replication of FVSKG2 in chicken embryo fibroblasts significantly at concentrations as low as 0.05 mM. The extinction of FVSKG2 was achieved during serial passage of the virus in chicken embryo fibroblasts at ≥0.05 mM ribavirin; however, the emergence of a mutagen-resistant virus was not observed until the eleventh passage. Further, no mutation was observed in 1,898 nucleotides of the FVSKG2 following its five passages in chicken embryo fibroblasts in the presence of 0.025 mM ribavirin. Ribavarin inhibited the FVSKG2 replication in chicken embryo fibroblasts primarily through IMPDH-mediated depletion of the Guanosine Triphosphate pool of cells. However, other mechanisms like ribavirin-mediated cytokine induction or possible inhibition of viral RNA-dependent RNA polymerase through its interaction with the enzyme’s active sites enhance the anti-IBDV effect. Ribavirin inhibits ds- RNA viruses, likely through IMPDH inhibition and not mutagenesis. The inhibitory effect may, however, be augmented by other non-mutagenic mechanisms, like induction of antiviral cytokines in chicken embryo fibroblasts or interaction of ribavirin with the active sites of RNA-dependent RNA polymerase of the virus.

Skatole (3-methylindole) is a heterocyclic compound naturally found in the feces of vertebrates and is produced by certain flowers. Skatole has been used in specific products of the perfume industry or as a flavor additive in ice cream. Additionally, skatole is formed by tryptophan pyrolysis of tobacco and has been demonstrated to be a mutagen. Skatole-induced pulmonotoxicity was reliably described in ruminants and rodents, but no studies have been conducted in humans. Initially, we provide basic knowledge and a historical overview of skatole. Then, skatole bacterial formation in the intestine is described, and the importance of the microbiome during this process is evaluated. Increased skatole concentrations could serve as a marker for intestinal disease development. Therefore, the human molecular targets of skatole that may have significant effects on various processes in the human body are described. Ultimately, we suggest a link between skatole intestinal formation in humans and skatole-induced pulmonotoxicity, which should be explored further in the future. [Display omitted] • Skatole is a naturally occurring compound that we encounter on daily basis. • Skatole production by human gut bacteria was connected with dysbiosis. • Skatole activates AhR, PXR, some MAPKs (ERK, JNK, p38), and p53. • Skatole induces pulmonotoxicity via cytochrome P450-mediated metabolism. [ABSTRACT FROM AUTHOR]

In a companion paper, we demonstrated that the nucleoside analogue favipiravir (FAV) suppressed Zika virus (ZIKV) replication in three human-derived cell lines—HeLa, SK-N-MC, and HUH-7. Our results revealed that FAV's effect was most pronounced in HeLa cells. In this work, we aimed to explain variation in FAV activity, investigating its mechanism of action and characterizing host cell factors relevant to tissue-specific differences in drug effect. Using viral genome sequencing, we show that FAV therapy was associated with an increase in the number of mutations and promoted the production of defective viral particles in all three cell lines. Our findings demonstrate that defective viral particles made up a larger portion of the viral population released from HeLa cells both at increasing FAV concentrations and at increasing exposure times. Taken together, our companion papers show that FAV acts via lethal mutagenesis against ZIKV and highlight the host cell's influence on the activation and antiviral activity of nucleoside analogues. Furthermore, the information gleaned from these companion papers can be applied to gain a more comprehensive understanding of the activity of nucleoside analogues and the impact of host cell factors against other viral infections for which we currently have no approved antiviral therapies. [ABSTRACT FROM AUTHOR]

Genetic toxicology tests are used to categorize substances as genotoxic and potentially carcinogenic. In general, test results are designated as mutagenic, not mutagenic, or inconclusive and, depending on its potential use and applicable regulations, a mutagenic result can restrict or remove a substance from further development, or assign limits to its use. In these tests, mutation responses form a continuum without a clear delineation between an increase over the background, untreated, mutant frequency and a frequency that would define the test substance as a mutagen and a potential carcinogenic hazard. This situation is illustrated using the Salmonella mutagenicity (Ames) test which is the initial, and often only, test used to characterize substances as mutagenic or nonmutagenic. It has its widest use by industry and regulatory authorities to identify potential carcinogens among chemicals in development. The OECD Test Guideline No. 471 has been adopted by regulatory agencies internationally, and describes the minimum requirements for a negative response, but does not provide a specific approach for evaluating the test data. The most widely used criterion for making yes‐or‐no mutagenicity decisions is a 2‐ or 3‐fold increase over the background (solvent) mutant frequency. Other approaches rely on formal statistics and/or expert judgment. These approaches and recently proposed modifications are evaluated here. Recommendations are made that are in conformity with the OECD guideline and are based on biological relevance and the biology of the mutagenic response rather than on arbitrary decision points (e.g., ≥2‐fold increase or p ≤.05). [ABSTRACT FROM AUTHOR]

Induced plant mutation breeding plays a pivotal role in crop improvement for several plant species. Induced mutagenesis using physical mutagens is widely carried out across the globe for improving different target traits. Gamma rays are the most common physical mutagen employed for mutagenesis programs, however, due to its inherent properties, the DNA damage and hence mutation spectrum achieved is limited. Other radiation sources such as neutrons, have much denser energy deposition mechanisms, and hence potentially can be used as a mutagen in plant mutation breeding to achieve desired mutations with minimal background mutations. Thermal neutrons have not been widely studied for plant mutation breeding due to technical constraints in its availability. In the current study, we used a dedicated thermal neutron facility with minimal contamination of fast neutron and gamma rays, to irradiate wheat (HI-1605) and rice (TCDM-1) varieties. Radiosensitivity analysis was carried out for both the varieties, HI-1605 had GR50 dose of 17.7 Gy while GR30 dose of 9.1 Gy, TCDM-1 had GR50 at 22.5 Gy and GR30 at 14.9 Gy. Wheat variety HI-1605 had LD50 dose of 17.4 Gy compared to 17.6 Gy of TCDM-1. Overall, the study demonstrates the potential of thermal neutron for plant mutagenesis in wheat and rice and in the future may be extended to other crops. [ABSTRACT FROM AUTHOR]

Chemical and physical mutagens like sodium azide, H2O2 and UV light have a significant role in the metabolism of living organisms. Effect of these mutagens was recorded during the present work on lipid content of Oscillatoria sp. and Ulothrix sp. The algal species were subjected to the mutagens by adding them in culture media. Lipids were extracted by Microwave-assisted extraction using methanol, ethanol and chloroform. During the present work generally a significant effect of algal species and mutagens was observed. All the tested mutagen significantly affected the lipid content. A significant effect of solvent on lipid content of algal species was observed when the algae were extracted with different solvents after treatment with H2O2 and UV light however this effect was non-significant when algae were subjected to sodium azide. In general, the mutagen resulted in an increase in lipid content. In Oscillatoria sp. the lipid content was generally less as compared to Ulothrix sp. The highest lipid content of 0.5433±0.002 g100g-1 was recorded in Ulothrix sp. after 3 days stress of sodium azide stress followed by H2O2 treated (50mM) samples with a content of 0.5133±0.05g100g-1. In Oscillatoria sp. 15mM treatment for 3 days gave a lipid content of 0.3733±0.0001g100g-1 after 3 days. A reduction in fresh weights of both tested algal species was recorded after UV stress. The oil content also showed a significant reduction after UV exposure. GC-MS analysis of the transesterified lipids showed that different fatty acids show variation when algal samples were treated with mutagens. Hence this study is helpful in manipulation of algal oil for biodiesel production. [ABSTRACT FROM AUTHOR]

According to recent literature, genotoxicity is one of the important causes of infertility and the rising incidence of various cancers worldwide. DNA damage and its effect on DNA segregation are the mechanisms by which genotoxicity causes infertility or carcinogenesis. In this article, we discuss about genotoxicity and the various chemicals and environmental pollutants that cause genetic damage and their mechanisms of action. Hazardous effects of chemicals and pollutants can be evaluated by various genotoxicity and mutagenicity tests. These are important and initial steps in industrial development and the regulation of their effect on health. The detailed knowledge of the effects of genotoxins on fertility at the molecular, subcellular, cellular and tissue or organ system levels is crucial for a better understanding of occupational and environmental hazards and the need to find safe alternatives. In addition, new biomarkers using OMICS can render genotoxicity evaluation to decrease the infertility and cancer risk. [ABSTRACT FROM AUTHOR]

Sugar substitutes are mostly artificial, man-made industrial products used as additives in food and beverages. Most of these substances flow through the digestive tract and food chains, becoming emerging organic contaminants in various abiotic and biotic environmental media. Here, we predict the mutagenicity and carcinogenicity of commonly used sugar substitutes using in silico based methods. The simplified molecular-input line-entry system (SMILES) of sugar substitutes was obtained from the PubChem database for toxicity predictions. Here, sixteen sugar substitutes tested out of these four compounds Glucin (GLU), and 5-nitro-2-propoxyaniline (P-4000), SCL, Ace were predicted as mutagens by using in silico tools such as LAZAR, pKCSM, and Toxtree. Based on the predicted results GLU and P-4000 were predicted as carcinogenic sugar substitutes. Also the study conducted compound gene interaction network to identify the direct connection between sugar substitutes and its corresponding receptors., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The irradiation method has been widely used in treating food for its many advantages, perhaps giving inadequate attention toits dark side. Based on many scientific studies, irradiation has a direct impact on food components, affecting the food’s attributes. But could consuming irradiated food for a long period of time have adverse health effects? The aim of this paper is to provide a brief overview of the scientific background of the use of radiation in the food industry and its effects on human health.

Uniform and healthy seeds of green gram cv. Pratap (SG-1) were treated with two mutagens, gamma rays (physical mutagen) and EMS (chemical mutagen) alone and in combination. The two hundred forty M1 progenies were laid in randomized block design with three replications during Kharif, 2017 to raise M2 generation. Analysis of variance discloses significant differences among the treatments for all the eight characters studied. It was observed that in general, the combination dose, i.e., 200 Gy+0.2% EMS gave superior results in almost all the yield attributing characteristics. High heritability coupled with high genetic advance was recorded for seed yield per plant, which indicates the predominance of additive gene action. Number of pods per plant followed by pod length showed high significant positive correlation with seed yield per plant. The character number of pods per cluster had shown positive correlation with seed yield per plant, but path analysis revealed its negative direct effect on seed yield. [ABSTRACT FROM AUTHOR]

Most historiographies of the crossroads of environmental and reproductive health in 20th century start and end with the case of thalidomide. Despite its global scope, thalidomide today stands for sharp contrasts: in the numbers of victims, in institutional responses to the disaster, and also—more generally—in regulatory approaches to potential risks and national cultures of reproductive justice and disability rights. This paper takes a closer look at two countries that have been seen as emblematic of this divide in regulatory frameworks, despite similarities and interconnections in other areas, such as (pharma)industrial production, science, and robust feminist environmental health movements: the U.S. and West Germany. It argues that thalidomide needs to be historically contextualized within a broad framework of concepts and models of environment from research on exogenous reproductive effects. To do so, it reconstructs what counted as environment in research on reproductive health and birth defects in these two national settings in the postwar decades. It looks at transformations made across multifaceted initiatives, studying collective landscapes and workplaces as potentially dangerous "outer worlds," as well as smaller scale and more individualized environments, i.e., the maternal metabolism, uterus, lifestyle, or social interactions. The article thereby aims to explicate concepts and debates about the environment that influenced later national divisions in politics of science and technology, hinting of the democratic challenges these posed. [ABSTRACT FROM AUTHOR]

Wheat, which is scientifically known as Triticum aestivum L., is a very nutritious grain that serves as a key component of the human diet. The use of mutation breeding as a tool for crop improvement is a reasonably rapid procedure, and it generates a variety that may be used in selective breeding programs as well as functional gene investigations. The present experiment was used to evaluate the potential application of a conventional chemical mutagenesis technique via sodium azide (NaN3) for the germination and seedling growth stage in wheat. Experiments with NaN3 mutagenesis were conducted using four different treatment periods (0, 1, 2, and 3 h) and five different concentrations (0, 0.5, 1, 1.5, and 2 mM). The genomic instability and cytosine methylation of wheat using its seeds were investigated after they were treated. In order to evaluate the genomic instability and cytosine methylation in wheat that had been treated, interprimer binding site (iPBS) markers were used. The mutagenic effects of NaN3 treatments had considerable polymorphism on a variety of impacts on the cytosine methylation and genomic instability of wheat plants. The results of the experiment showed considerable changes in the iPBS profiles produced by the administration of the same treatments at different dosages and at different times. Coupled restriction enzyme digestion interprimer binding site (CRED-iPBS) assays identified changes in gDNA cytosine methylation. The highest polymorphism value was obtained during 1 h + 2 mM NaN3, while the lowest (20.7%) was obtained during 1 h + 1.5 mM NaN3. Results showed that treatments with NaN3 had an effect on the level of cytosine methylation and the stability of the genomic template in wheat plants in the germination stage. Additionally, an integrated method can be used to for mutation-assisted breeding using a molecular marker system in wheat followed by the selection of desired mutants.

The shoot and fruit borer has asserted itself as a severe pest of eggplant. In vitro mutagenesis is an excellent method for producing mutants resistant to biotic and abiotic stresses. This study aimed to create eggplant mutants that were resistant to shoot and fruit borer infestation. In the Murashige and Skoog (MS) medium, two genotypes, including a landrace, were treated with varying amounts of EMS. Among the treatments, MS medium supplemented with 2% EMS demonstrated the most favorable effect. Explant performance dropped by up to 1.5% with an increase in EMS in the medium. The 2% EMS dose was appropriate for in vitro mutant eggplant development, but the higher dose was extremely damaging. EMS made several mutants sterile. Three landrace mutants were insect-resistant. Total phenols, leaf chlorophylls A and B, antioxidants, and solasodine were abundant in these genotypes. Correlation studies found a link between affected fruits and shoots and total phenols, antioxidants, and solasodine. Solasodine was shown to be related to chlorophylls A and B. The eggplant shoot and fruit borer infestation rate can be reduced by increasing these specific biochemical properties. [ABSTRACT FROM AUTHOR]

Mutation refers to unexpected heritable change in the phenotype of an individual. In molecular biology mutation refers permanent and relatively rare change in the number or sequence of nucleotides. The silkworm Bombyx mori, is one of the important insect genetic model for the order Lepidoptera. India is the second largest silk producer of the world, which produces both mulberry and non mulberry silk .Use of mutagens can be a useful tool in exploring the genetic variations in silkworm for both quantitative and qualitative characters in mutation breeding. Several attempts have been made to induce beneficial mutations in the silkworm and some have proved to be useful to the sericulture sector. Mutation breeding by using appropriate mutagens leads to formation of new breed with good quantitative and qualitative characters, which are very much essential for overall development of the Indian silk industry. [ABSTRACT FROM AUTHOR]

Grass pea (Lathyrus sativus L.) is an important protein-rich annual legume crop that can survive harsh environment conditions. Genetic improvement of grass pea is highly important for expanding its production, and mutation breeding can be a valuable tool in creating additional genetic variability. In the present study, we treated totally 3000 seeds of widely cultivated grass pea cultivar, Gürbüz-2001, with two different concentrations (0.5% and 1%) of mutagen EMS for 4 hours. The germination rates were calculated as 71.6% (1074 plants) and 42.4% (636 plants) for 0.5% and 1% EMS concentrations in M1 generation, respectively. We identified several mutant phenotypes such as seedling growth defects, abnormal branching, chlorophyll mutants, absence of flowering, and sterility in M1 and M2 populations. A total of 40 mutant plants which were superior than control variety in terms of vegetative components from M2 population were selected for agronomic, quality and forage traits analysis. Plant height of mutant lines ranged from 48 (GMP29) to 164 cm (GMP4), with an average value of 109.7 cm. One of the most interesting features of some mutant lines was the significant increase in 1000-seed weight over the control value, contributing to higher yield. The seed yield ranged from 7.19 to 87.18 g, and the lines GPM6 and GMP11 showed superior values compared to the control (13.6 g), indicating the positive effect of mutation in obtaining desired traits. There were promising mutants that showed higher levels of protein content among mutated lines. The β-ODAP (β-N-Oxalyl-l-α,β-diaminopropionic acid) content of grass pea seeds ranged from 0.139% to 7.39% in selected M2 population, while the control cultivar was 0.523%. GPM6 and GPM11 were important for forage breeding with their high crude protein content, low ADF (acid detergent fiber) and NDF (neutral detergent fiber) ratios, as well as high seed and biological yield. The beneficial traits of these mutants obtained in this study should be followed to integrate as genetic resources for use in grass pea improvement programs. [ABSTRACT FROM AUTHOR]

Abstract Background A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this “DNA adductome approach” in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. Aim Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. Materials and methods From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. Results Seven DNA adducts, including modified bases, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2′-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2′-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2′-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. Conclusions We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.

APOBEC3B enzymes are endogenous carcinogenic mutagens. Metastatic urothelial carcinomas often harbor APOBEC3B-mediated mutations in which tCw to T or G substitution occurs. Here, we evaluated patient survival and CD8+ T-cell density according to APOBEC3B expression in patients with metastatic urothelial carcinoma who underwent cytotoxic chemotherapy. We performed a retrospective study on 94 patients with urothelial carcinoma who were treated with first line palliative chemotherapy. APOBEC3B expression and CD8+/CD3+ ratio of tumor-infiltrating lymphocytes were evaluated using immunohistochemistry. Kaplan–Meier survival curves were generated and the log-rank test was employed. The association between APOBEC3B expression and tumor-infiltrating lymphocytes was analyzed using Pearson’s chi-squared test. High APOBEC3B expression was detected in 71 of the 94 patients (75.5%). The median overall survival was longer in patients with high APOBEC3B expression (15 months) than in those with low expression (p = 0.045). The hazard ratio obtained based on the Cox regression analysis was 0.292 (95% confidence interval 0.118–0.723, p = 0.008). APOBEC3B expression was associated with the CD8+/CD3+ ratio (2.914, 95% confidence interval 1.030–8.249, p = 0.039). Collectively, APOBEC3B expression was an independent prognostic factor in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy. Tumor-infiltrating cytotoxic T cells were associated with APOBEC3B expression.

Background: The goal of genetic breeding is to select variants with mutations that are related to expected traits, such as fast growth. Artificial induction has been widely used to obtain strains with more mutations for further selection. Ethylmethylsulfone (EMS) is one of the most commonly used chemical mutagens in plant and microorganism breeding. However, the application of EMS mutagenesis in shellfish has not been reported. The aim of this study is to evaluate the potential use of EMS as a mutagen in scallop breeding, especially in characterization of mutations in growth-related genes. Results: Our results indicated that hatching of about 50% of fertilized eggs was blocked by treatment with 20 mM EMS for 3 h and the resulted larvae developed normally into adult stages. We then evaluated the mutagenic effects of EMS by sequencing the genomes of 4 adult scallops from the control group and 12 from the treatment group at 8 months after fertilization. On average, after removing shared types of mutations, there were 1,151,380 ± 258,188 SNPs (Single Nucleotide Polymorphisms) and 229,256 ± 51,714 InDels (insertion-deletion) in each animal in the EMS treatment group, while there were only134841 ± 10,115 SNPs and 42,605 ± 5,136 InDels in the control group. The average mutation rate in the genome of the EMS treatment group (0.0137 ± 0.0013%) was about 9 times that of the control group (0.0015 ± 0.0002%). GO (Gene Ontology) annotation and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses revealed that mutations induced by EMS occurred evenly in most biological processes, cellular components and functions, as well in most pathways. However, significant lower percentage of mutations were found in the exonic region, in non-synonymous or Stopgain/Stoploss SNPs and in coding domains, suggesting apparent DNA repair or selection during grow-out stage. Analyses of the growth-related genes with mutations indicated that mutations in MFS (Major Facilitator Superfamily) and Tubulin were only found in the large-sized group (Five largest scallops: Treated-1, Treated-2, Treated-3, Treated-4, and Treated-5) and Homeobox and Socs (Suppressor of cytokine signaling) only in the small group (Two smallest scallops: Treated-11 and Treated-12). These results suggested that these genes may be involved in the regulation of growth in these animals, although further verification is certainly warranted. Conclusion: Treatment of fertilized eggs with 20 mM EMS for 3 h induced 9 times more mutations in scallop genomes. We found that mutations in MFS and Tubulin may be related to fast growth in the large-sized group and those mutations in Homeobox and SOCs may be involved in the slow growth in the small-sized scallops. EMS can be used to accelerate selection of economically important traits in molluscs. [ABSTRACT FROM AUTHOR]

Background: Research on the status of many chemicals used in the semiconductor industry is needed. The purpose of this study was to describe the overall status of chemical use in the semiconductor industry in Korea and to examine it from a health perspective. Methods: Data on the status of chemical use and safety data sheets at 11 of 12 major semiconductor workplaces in Korea were collected. The number of chemical products and chemical constituents, quantities of chemicals, and trade secret ingredients used, as well as the health hazards were examined. Results: On average, 210 chemical products and 135 chemical constituents were used at the surveyed workplaces. Among all chemical products, 33% (range: 16–56%) contained at least one trade secret ingredient. Most of the trade secret ingredients were used in the photolithography process. Several carcinogens, including sulfuric acid, chromic acid, ethylene oxide, crystalline silica, potassium dichromate, and formaldehyde were also used. Only 29% (39 of 135) of the chemical constituents had occupational exposure limits, and more than 60% had no National Fire Protection Association health, safety, and reactivity ratings. Based on the aforementioned results, this study revealed the following. First, many chemical products and constituents are being used in the semiconductor industry and many products contained trade secret ingredients. Second, many products contained significant amounts of carcinogenic, mutagenic, and reproductive toxicant materials. Conclusion: We conclude that protecting workers in the semiconductor industry against harm from chemical substances will be difficult, due to widespread use of trade secret ingredients and a lack of hazard information. The findings of the status of chemical use and the health and safety risks in semiconductor industry will contribute to epidemiological studies, safe workplace, and worker health protection.

The objectives of our investigations are to describe the variation by muta-tions of stem architecture of the modern Ukrainian winter wheat varieties accord-ing to their interactions with mutagen nature, concentration and genotype-mutagen interaction specific. 7 modern Ukrainian winter wheat varieties and one line were treated by 1.4-bisdiazoatsetilbutan water solution at 0.1 and 0.2% concentrations. Types of visible mutations like as high and short stem, dwarfs and semi-dwarfs, changes in a waxy bloom, stem thickness have been investigated. New genetic- and breeding-value mutant lines have been obtained in terms of research program. Main components for mutation induction successful were geno-type-mutagen interaction and peculiarities of genotype as a subject of mutagen action (due to discriminant and factor analyses). By mutation occurs (in sense of mutation rate and spectra) genotypes can be subdivided on several groups. Effect of recurrent mutagenesis was identified as decrease of mutation rate under mutagen action by variety Kalinova, which obtained with same mutagen. Other geno-types reaction on mutagen action depends on genotype specific only, not kind of treatment. Bisdiazoatsetilbutan as a mutagens for creation new material by plant height and stem structure has been shown as less successful than gamma-rays and nitrosoalkylureas, but this mutagen may be used for special investigation by some types of mutation induction. But it was more specific in a mutagen-genotype interaction and more clearly demonstrate some effects of recurrent mu-tagenesis regarding nature of chemical agents. As for example action on variety Sonechko with great number of mutations by waxy bloom. These peculiarities may be caused by previous chemical mutagens damages of DNA in complex with recurrent action of bisdiazoatsetilbutan. Genotype-mutagen interaction and classification of mutant material are possible by rate of high and short stem, with and without waxy bloom forms. Concentration affected on rate of high stem forms. Mutagen cannot induce dwarf and semi-dwarf forms in significant amount and completely unpromising in this regard. Our research will be further focused on transformation of scientific and technological achievements and mutagenic mech-anism of bisdiazoatsetilbutan on plant at the molecular level in the recent future.

Background: The goal of genetic breeding is to select variants with mutations that are related to expected traits, such as fast growth. Artificial induction has been widely used to obtain strains with more mutations for further selection. Ethylmethylsulfone (EMS) is one of the most commonly used chemical mutagens in plant and microorganism breeding. However, the application of EMS mutagenesis in shellfish has not been reported. The aim of this study is to evaluate the potential use of EMS as a mutagen in scallop breeding, especially in characterization of mutations in growth-related genes.Results: Our results indicated that hatching of about 50% of fertilized eggs was blocked by treatment with 20 mM EMS for 3 h and the resulted larvae developed normally into adult stages. We then evaluated the mutagenic effects of EMS by sequencing the genomes of 4 adult scallops from the control group and 12 from the treatment group at 8 months after fertilization. On average, after removing shared types of mutations, there were 1,151,380 ± 258,188 SNPs (Single Nucleotide Polymorphisms) and 229,256 ± 51,714 InDels (insertion-deletion) in each animal in the EMS treatment group, while there were only134841 ± 10,115 SNPs and 42,605 ± 5,136 InDels in the control group. The average mutation rate in the genome of the EMS treatment group (0.0137 ± 0.0013%) was about 9 times that of the control group (0.0015 ± 0.0002%). GO (Gene Ontology) annotation and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses revealed that mutations induced by EMS occurred evenly in most biological processes, cellular components and functions, as well in most pathways. However, significant lower percentage of mutations were found in the exonic region, in non-synonymous or Stopgain/Stoploss SNPs and in coding domains, suggesting apparent DNA repair or selection during grow-out stage. Analyses of the growth-related genes with mutations indicated that mutations in MFS (Major Facilitator Superfamily) and Tubulin were only found in the large-sized group (Five largest scallops: Treated-1, Treated-2, Treated-3, Treated-4, and Treated-5) and Homeobox and Socs (Suppressor of cytokine signaling) only in the small group (Two smallest scallops: Treated-11 and Treated-12). These results suggested that these genes may be involved in the regulation of growth in these animals, although further verification is certainly warranted.Conclusion: Treatment of fertilized eggs with 20 mM EMS for 3 h induced 9 times more mutations in scallop genomes. We found that mutations in MFS and Tubulin may be related to fast growth in the large-sized group and those mutations in Homeobox and SOCs may be involved in the slow growth in the small-sized scallops. EMS can be used to accelerate selection of economically important traits in molluscs.

In a companion paper, we demonstrated that the nucleoside analogue favipiravir (FAV) suppressed Zika virus (ZIKV) replication in three human-derived cell lines—HeLa, SK-N-MC, and HUH-7. Our results revealed that FAV’s effect was most pronounced in HeLa cells. In this work, we aimed to explain variation in FAV activity, investigating its mechanism of action and characterizing host cell factors relevant to tissue-specific differences in drug effect. Using viral genome sequencing, we show that FAV therapy was associated with an increase in the number of mutations and promoted the production of defective viral particles in all three cell lines. Our findings demonstrate that defective viral particles made up a larger portion of the viral population released from HeLa cells both at increasing FAV concentrations and at increasing exposure times. Taken together, our companion papers show that FAV acts via lethal mutagenesis against ZIKV and highlight the host cell’s influence on the activation and antiviral activity of nucleoside analogues. Furthermore, the information gleaned from these companion papers can be applied to gain a more comprehensive understanding of the activity of nucleoside analogues and the impact of host cell factors against other viral infections for which we currently have no approved antiviral therapies.

Mycoplasmas, autonomously culturable bacteria with the smallest genome, are an important organism to understand the minimal form of life. Mutagenesis using mutagens is a useful methodology for understanding the essential regions of genomic information. Ultraviolet light (UV) and trimethyl psoralen (TMP) are mutagens known to induce various mutations; the latter is reported to specifically induce deletions in nematodes. However, their mutagenic effects on mycoplasma are not known. Here, we exposed Metamycoplasma salivarium to UV-C light or TMP and UV-A as mutagens, and analyzed the mutational pattern after serial cultivation ranging from 34 to 56 rounds for different lineages. Our results showed that more deletions, but fewer point mutations, were induced with TMP and UV-A than with UV-C, indicating the usefulness of TMP in inducing deletions. In addition, we compared our results with mutational data from other studies, which suggested that the combination of TMP and UV-A or UV-C exposure both induced point mutations that were highly biased toward C→T and G→A transitions. These data provide useful basic knowledge for mutational studies on M. salivarium.

The mutagenic effects of ionizing radiation have been used for decades to create novel variants in experimental populations. Fast neutron (FN) bombardment as a mutagen has been especially widespread in plants, with extensive reports describing the induction of large structural variants, i.e., deletions, insertions, inversions, and translocations. However, the full spectrum of FN-induced mutations is poorly understood. We contrast small insertions and deletions (indels) observed in 27 soybean lines subject to FN irradiation with the standing indels identified in 107 diverse soybean lines. We use the same populations to contrast the nature and context (bases flanking a nucleotide change) of single-nucleotide variants. The accumulation of new single-nucleotide changes in FN lines is marginally higher than expected based on spontaneous mutation. In FN-treated lines and in standing variation, C!T transitions and the corresponding reverse complement G!A transitions are the most abundant and occur most frequently in a CpG local context. These data indicate that most SNPs identified in FN lines are likely derived from spontaneous de novo processes in generations following mutagenesis rather than from the FN irradiation mutagen. However, small indels in FN lines differ from standing variants. Short insertions, from 1 to 6 bp, are less abundant than in standing variation. Short deletions are more abundant and prone to induce frameshift mutations that should disrupt the structure and function of encoded proteins. These findings indicate that FN irradiation generates numerous small indels, increasing the abundance of loss-offunction mutations that impact single genes. [ABSTRACT FROM AUTHOR]

Abstract Mutations are changes in the genetic material that may be transmitted to subsequent generations. Mutations appear spontaneously in nature and are one of the underlying driving forces of evolution. In plants, in vivo and in vitro random mutagenesis relies on the application of physical and chemical mutagens to increase the frequency of mutations thus accelerating the selection of varieties with important agronomic traits. The European Commission has requested EFSA to provide a more detailed description of in vivo and in vitro random mutagenesis techniques and the types of mutations and mechanisms involved, to be able to conclude on whether in vivo and in vitro random mutagenesis techniques are to be considered different techniques. To address the European Commission request, a literature search was conducted to collect information on the random mutagenesis techniques used in plants both in vivo and in vitro, on the type of mutations generated by such techniques and on the molecular mechanisms underlying formation of those mutations. The GMO Panel concludes that most physical and chemical mutagenesis techniques have been applied both in vivo and in vitro; the mutation process and the repair mechanisms act at cellular level and thus there is no difference between application of the mutagen in vivo or in vitro; and the type of mutations induced by a specific mutagen are expected to be the same, regardless of whether such mutagen is applied in vivo or in vitro. Indeed, the same mutation and the derived trait in a given plant species can be potentially obtained using both in vivo and in vitro random mutagenesis and the resulting mutants would be indistinguishable. Therefore, the GMO Panel concludes that the distinction between plants obtained by in vitro or in vivo approaches is not justified.

Mutations are changes in the genetic material that may be transmitted to subsequent generations. Mutations appear spontaneously in nature and are one of the underlying driving forces of evolution. In plants, in vivo and in vitro random mutagenesis relies on the application of physical and chemical mutagens to increase the frequency of mutations thus accelerating the selection of varieties with important agronomic traits. The European Commission has requested EFSA to provide a more detailed description of in vivo and in vitro random mutagenesis techniques and the types of mutations and mechanisms involved, to be able to conclude on whether in vivo and in vitro random mutagenesis techniques are to be considered different techniques. To address the European Commission request, a literature search was conducted to collect information on the random mutagenesis techniques used in plants both in vivo and in vitro, on the type of mutations generated by such techniques and on the molecular mechanisms underlying formation of those mutations. The GMO Panel concludes that most physical and chemical mutagenesis techniques have been applied both in vivo and in vitro; the mutation process and the repair mechanisms act at cellular level and thus there is no difference between application of the mutagen in vivo or in vitro; and the type of mutations induced by a specific mutagen are expected to be the same, regardless of whether such mutagen is applied in vivo or in vitro. Indeed, the same mutation and the derived trait in a given plant species can be potentially obtained using both in vivo and in vitro random mutagenesis and the resulting mutants would be indistinguishable. Therefore, the GMO Panel concludes that the distinction between plants obtained by in vitro or in vivo approaches is not justified. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death all around the world. It is a group of diseases characterized by abnormal and uncontrollable division of cells leading to severe health conditions and fatality if remains undiagnosed till later stages. Cancer can be caused due to mutation or sudden alterations by effect of certain external agents. Agents that can cause sudden alterations in the genetic content of an individual are known as mutagens. Mutations can lead to permanent changes in the genetic constituency of an individual and possibly lead to cancer. Mutagenic agents that possess the capacity to induce cancer in humans are called carcinogens. Carcinogens may be naturally present in the environment or generated by anthropogenic activities. However, with the progress in molecular techniques, genetic and/or epigenetic mechanisms of carcinogenesis of a wide range of carcinogens have been elucidated. Present review aims to discuss different types of environmental carcinogens and their respective mechanisms responsible for inducing cancer in humans. [ABSTRACT FROM AUTHOR]

We are exposed to various chemical compounds present in the environment, cosmetics, and drugs almost every day. Mutagenicity is a valuable property that plays a significant role in establishing a chemical compound's safety. Exposure and handling of mutagenic chemicals in the environment pose a high health risk; therefore, identification and screening of these chemicals are essential. Considering the time constraints and the pressure to avoid laboratory animals' use, the shift to alternative methodologies that can establish a rapid and cost-effective detection without undue over-conservation seems critical. In this regard, computational detection and identification of the mutagens in environmental samples like drugs, pesticides, dyes, reagents, wastewater, cosmetics, and other substances is vital. From the last two decades, there have been numerous efforts to develop the prediction models for mutagenicity, and by far, machine learning methods have demonstrated some noteworthy performance and reliability. However, the accuracy of such prediction models has always been one of the major concerns for the researchers working in this area. The mutagenicity prediction models were developed using deep neural network (DNN), support vector machine, k-nearest neighbor, and random forest. The developed classifiers were based on 3039 compounds and validated on 1014 compounds; each of them encoded with 1597 molecular feature vectors. DNN-based prediction model yielded highest prediction accuracy of 92.95% and 83.81% with the training and test data, respectively. The area under the receiver's operating curve and precision-recall curve values were found to be 0.894 and 0.838, respectively. The DNN-based classifier not only fits the data with better performance as compared to traditional machine learning algorithms, viz., support vector machine, k-nearest neighbor, and random forest (with and without feature reduction) but also yields better performance metrics. In current work, we propose a DNN-based model to predict mutagenicity of compounds. [ABSTRACT FROM AUTHOR]

This study mathematically and computationally analyzes the effects of a combination of a chemical mutagen and an immune checkpoint inhibitor to develop an alternative anti-retroviral therapy. First, we addressed how the condition for HIV cure depends the efficacy of these two agents. We concluded that HIV cure only depends on the efficacy of the chemical mutagen, not on the immune checkpoint inhibitor. In other words, the combinatorial use of the two agents did not affect the necessary condition for the HIV "cured state". On the other hand, we confirmed the effectiveness of the combinatorial treatment with the two agents on the eradication of productively infected cells. Computer simulations clarified that combination treatment with the two agents enables eradication of productively infected cells faster than does treatment with the mutagen alone. [ABSTRACT FROM AUTHOR]

Background: A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this "DNA adductome approach" in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. Aim: Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. Materials and methods: From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. Results: Seven DNA adducts, including modified bases, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2′-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2′-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2′-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. Conclusions: We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future. [ABSTRACT FROM AUTHOR]

There are many pests and diseases that cause yield and quality loss which limits potato production in Turkey and in the world. One of diseases is Rhizoctonia solani (telemorph: Thanatephorus cucumeris) which gives rise to black scurf and stem canker of potato. In this experiment, potato cv. Alanso plants were treated with Ethyl methanesulfonate (EMS) at different concentrations (0, 20mM, 50mM, 75mM, 100mM) and different pre-soaking times (0, 10, 20 min.) under in vitro conditions. EMS treated plants in vitro were inoculated with Rhizoctonia solani after four consecutive subcultures. The survival plant rates were established after 15 days. Some plant parameters (plant nodes number, plant size, leaf number etc.) were recorded and plant parameters were compared with the negative control. The highest survival rate of the plants (32%) was determined in the 50 mM EMS for 10 min. application, while the lowest survival rate of the plants (10%) was determined at 75 mM for 20 min. application of EMS. The survival rate of positive control plants determined as 4% (P=0.05). The highest plant size was determinated at 50 mM dose for 20 minute, the highest number of plant root was determinatedat 75mM dose for 20 minute. The EMS mutagenic applications in potato plants have been effective in improving the tolerance of plants to R. solani. These resistant mutants against R. solani can be used in a hybridization program to produce better recombinants. [ABSTRACT FROM AUTHOR]

The rodent Pig‐a assay is a flow cytometric, phenotype‐based method used to measure in vivo somatic cell mutation. An Organization for Economic Co‐operation and Development (OECD) test guideline is currently being developed to support routine use of the assay for regulatory purposes (OECD project number 4.93). This article provides advice on best practices for designing and conducting rodent Pig‐a studies in support of evaluating test substance safety, with a focus on the rat model. Various aspects of assay conduct, including laboratory proficiency, minimum number of animals per dose group, preferred treatment and blood sampling schedule, and statistical analysis are described. [ABSTRACT FROM AUTHOR]

Eight mutant lines developed through mutation breeding technique using chemical mutagen along with parent line (Sadori) were evaluated at NIA, experimental farm. Quantitative and qualitative traits were analyzed statistically. The chemical mutagen Ethyle Methane Sulphonate (EMS) was used at the rate of 0.03%. The mutant lines (viz. NIA-M5, NIA-M10, NIA-M16, NIA-M20, NIA-M23, NIA-M29, NIA-M33 and NIA-M35) with parent Sadori were included in this study. The results revealed that three mutants (NIA-M20, NIA-M35 and NIA-M5) took (7.2%, 8.1% and 8.1%) higher plant height than parent (111 cm), two mutants (NIA-M5 and NIA-M20) obtained (36.8% and 42.1%) more sympodial branches plant-1 than parent (19.0). Three mutants (NIA-M20, NIA-M5 and NIA-M10) produced (16.8%, 22.4.0% and 25.4%) more number of bolls plant-1 than parental line (67.0). Five mutants (NIA-M5, NIA-M35, NIA-M20, NIA-M23 and NIA-M29) had higher fiber length (mm) (10.2%, 8%, 5.7%, 5% and 4.0%) as compared parent Sadori (28.0 mm). Two mutants (NIA-M20 and NIA-M29) showed higher fiber strength (g/tex) (5.5% and 8.3%) than parent (34.4%). Two mutants (NIA-M5 and NIA-M20) produced higher seed-cotton yield kg ha-1 (24.0% and 25.4%) over parent Sadori (3563 kg ha-1). The selected mutant lines on the basis of higher seed-cotton yield (kg ha-1) and enhanced fiber length (mm) compared to parent (Sadori) will be promoted in preliminary yield trials. Heritability and genetic advance were noted for early days to maturity, higher plant height (cm), sympodial branches plant-1, lengthy fiber (mm), bolls plant-1 and seed-cotton yield (kg ha-1).

The employers responsibilities for the assessment of occupational exposure to cytostatics in the workplace were analyzed in the light of existing legal regulations. Cytostatics may pose a threat to health and life of workers taking care of patients treated oncologically, i.e., pharmacists, physicians, nurses and other personnel. The significant scale of occupational exposure to cytostatics in Poland is confirmed by the data collected in the Central Register of Data on Exposure to Carcinogenic or Mutagenic Substances, Mixtures, Agents or Technological Processes, maintained by the Nofer Institute of Occupational Medicine, Łódź, Poland. The issue of occupational risk assessment of exposure to cytostatics gives raise to numerous concerns. Polish regulations concerning health protection of employees occupationally exposed to cytostatics are not unequivocal, as they are derived from different areas of the law, especially those applying to hazard classification, labeling and preparation of safety data sheets for cytostatics. There are neither binding occupational exposure limits legally set for active compounds of antineoplastic drugs nor methods for monitoring of these substances concentrations in a worker’s breathing zone and biological material. This prevents the employer to carry out the correct assessment of occupational exposure, the results of which are the basis for preparing the proper preventive strategy. In this article the consequences of amendments to the European chemical legislation for employers responsible for adequate protection of health and life of employees exposed to cytostatics, were discussed, as well as some legal changes aimed at a better health and life protection of workers exposed to cytostatics in a workplace were proposed. Med Pr 2018;69(1):77–92

Abstract An organic compound known as 5-hydroxymethylfurfural (HMF) is formed from reducing sugars in honey and various processed foods in acidic environments when they are heated through the Maillard reaction. In addition to processing, storage conditions affect the formation HMF, and HMF has become a suitable indicator of honey quality. HMF is easily absorbed from food through the gastrointestinal tract and, upon being metabolized into different derivatives, is excreted via urine. In addition to exerting detrimental effects (mutagenic, genotoxic, organotoxic and enzyme inhibitory), HMF, which is converted to a non-excretable, genotoxic compound called 5-sulfoxymethylfurfural, is beneficial to human health by providing antioxidative, anti-allergic, anti-inflammatory, anti-hypoxic, anti-sickling, and anti-hyperuricemic effects. Therefore, HMF is a neo-forming contaminant that draws great attention from scientists. This review compiles updated information regarding HMF formation, detection procedures, mitigation strategies and effects of HMF on honey bees and human health.