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A new quantitative method is reported for the detection of prophage induction which directly measures the excision of the prophage from the host chromosome. This new method is based on the use of two converging oligonucleotides, corresponding to each side of the a11P sequence of a temperature phage to amplify the intervening DNA segment by real time PCR.

Research has been conducted on chromiumchromium(VI) mutagenicity. The study of mutational spectrum and the role of oxidative damage and chromium-DNA adducts in chromium(VI) mutagenicity activated by biologically relevant concentrations of ascorbate has been carried out, and the differences in genotoxic and mutagenic responses to chromium-DNA adducts between bacterial and human cells have been investigated and discussed.

Research has been conducted on acrolien, a member of the alpha, beta-unsaturated aldehyde family. The role of alpha-OH-1,N (super)2 ?propanodeoxyguanosine adduct in the genotoxicity of this acrolein has been investigated via comparison of alpha-OH-1,N (super)2 ?propanodeoxyguanosine, gamma-OH-1,N (super)2 ?propanodeoxyguanosine and propanodeoxyguanosine by in vitro primer extension studies and in human cells and the details are reported.

Research has been conducted on the functional Cdc2-cyclin B kinase complex. The evidence that this complex is required for the homologous recombination and is necessary to protect cells from the ionizing radiation genotoxic consequences is presented.

An Arabidopsis mutant (mkp1) hypersensitive to genotoxic stress treatments because of disruption of mitogen-activated protein kinase phosphatase (AtMKP) has been identified. A gene that encodes an Arabidopsis homolog of AtMKP is necessary for Arabidopsis genotoxic stress relief. It appears that the MAP kinase cascade has a vital role in genotoxic stress signaling in plants and that AtMKP1 is a vital regulator of MAP kinase activity in vivo. It probably determines outcome of the cellular reaction and the level of genotoxic resistance.

Results point out that 30% of the urinary metabolites contain derivatives of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid which, arise from benzo[alpha]pyrene (BP) by ring opening pathway. Data reveal that anhydride of the derivative induces DNA dmages thereby suggesting indirect toxicity effect of BP.

Higher plants used extensively in traditional medicines are increasingly being screened for their role in modulating the activity of environmental genotoxicants. The property of preventing carcinogenesis has been reported in many plant extracts. The observation of a close association between carcinogenesis and mutagenesis has extended the survey to include plant extracts and plant products able to modify the process of mutagenesis, which involves alteration in the genetic material. Natural plant products may, apart from inducing mutations, modify the action of other known mutagens on the living organisms by 1) activating the existing mutagens within the cell, 2) inhibiting the production of mutagens in the cell, 3) synergising the activity of existing mutagens, or 4) activating the promutagens within the cell into mutagens. This review deals with data obtained in the course of research on the modulatory effects of plant extracts on mutagenesis and clastogenesis, two genotoxic phenomena associated with carcinogenesis. In screening for antimutagenic effects, extracts of different plant parts have been used, ranging from leafy vegetables, fruits, and underground storage organs to whole plants. The extracts were prepared mainly in water or organic solvents. Several of these assays have indicated the involvement of certain factors that are intrinsic components of the extracts, ranging from specific compounds like ascorbic acid to vegetable fibres which could act as nonspecific redox agents, free radical scavengers, or ligands for binding metals or toxic principles. The possible ways in which inhibitors of mutagenesis can act include the inhibition of interaction between genes and biochemically reactive mutagens and the inhibition of metabolic activation of indirectly acting mutagens. The effects of toxicants can be observed at the level of chromosomes (clastogenesis) through alterations in chromosome structure (chromosomal aberrations) and number (aneuploidy, polyploidy). A wide range of short-term and long-term screening procedures is available. The most common ones use higher plants or rodents in vivo as test systems for monitoring chromosomal aberrations. Experiments with a number of crude vegetable and fruit extracts have demonstrated their anticlastogenic activities against known cytotoxic agents. The individual components of the extracts - e.g., sulfhydryl and flavonoid compounds, gallic acid, ellagic acid, mucic acid, citric acid, reducing sugars, tannin - are observed to have an additive interaction with the major constituents chlorophyll and ascorbic acid, when modulating the effects of the clastogens. Under certain conditions, plant products may induce mutagenic effects, due to the presence of multiple biological properties. Some inhibitors can stimulate simultaneously both enhancing and detoxifying mechanisms, e.g., inducers of coordinated enzyme activities. Many oxidants can, depending on the redox potential, either accept or donate electrons, rendering them protective or harmful. Plants also play an active role in the accumulation, metabolism, and environmental distribution of xenobiotics. The property of plants to activate promutagens that may enter the food chain is of great significance in view of the large number and types of chemicals to which the plants are exposed. A promutagen is a chemical that is not mutagenic itself but that can be biologically transformed by a plant system into a mutagen. Several methods for studying promutagens from plants were developed both in vivo and in vitro, including plant cell-free systems. Both mutagens and antimutagens can be extracted from the same plant extract depending on the nature of solvents used for extraction. Interaction between inhibitors may lead to synergistic effects. Such combined action may take place through the different inhibitors acting at different levels or being localised at different cellular areas. The greater protection afforded by crude plant extract as compared with an equivalent amount of the purified or synthetic ingredients, as observed with Phyllanthus emblica L. and Beta vulgaris L. var. benghalensis Hort., may be related to this phenomenon. Specific biological action of a drug is due to its specific binding to a functional molecular receptor. In complex plant extracts, the variable observed effects can be attributed to the many chemically reactive species that are formed during the processing and ingestion of the extract, which could act as non-specific redox agents, scavengers of free radicals, and ligands for binding to toxicants. The final effects are obviously the outcome of interactions between the components and their individual and collective interaction with the toxicant. The specificity and efficacy of such responses will be influenced also by the physiological factors influencing the plants and the process of administration of the extract. In utilizing pharmacologically active herbs, both beneficial and potential adverse effects must be taken into account. The actual dose and form of the plant also need to be worked out., II. Introduction Traditional medicines based on plants have been useful in discovering new drugs from natural products, in helping to identify new biochemical loci for drug action, and in developing [...]

Toxicity induction in Escherichia coli in response to chemical toxicants, when regulated by a uspA'::lux fused gene, exhibits clear distinctions among toxicants. This differential response is useful to detect toxicants. Toxicant response of this gene is similar to that of the thermal shock-responsive gene fusion grpE'::lux, except that the grpE'::lux strain exhibits a greater magnitude of induction.

A study using NMR was conducted to determine the oncogenetic activity of aflatoxin B1 (AFB1), a common fungal metabolite found contaminating food and cosmetic products. Aflatoxin B1 is metabolized by cytochrome P450 into AFB1 exo-8,9-epoxide, which reacts with the N7 of guanine to form trans-8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 adduct. The aflatoxin moiety and the extra adenosine nucleotide which it causes to be inserted in the complementary DNA strand form a stable intrahelical structure in DNA which could be a cause of oncogenesis.

A study using NMR examination of oligodeoxynucleotides of the human n-ras protooncogene was conducted to determine the oncogenic properties of styrene oxide, a by-product of plastics and resin manufacturing. The results show that styrene oxide forms adducts at codon 61 of the human n-ras, leading to protooncogene activation, which is an early stage of carcinogenesis.

Until recently, the mechanism of carcinogenesis has been regarded as a two-stage phenomenon involving damage to the genetic material, which initiates the process, followed by a cell-division stimulus, which promotes the development of the tumour. However, exposure to some chemicals has been shown to result in carcinogenesis without involvement of the initiation step. The mechanism of non-genotoxic carcinogenesis is not fully understood, but is believed to involve stimulation of cell division with a consequent increased probability of a mutation occurring spontaneously. In this article, Ian Shaw and Huw Jones review the theories of non-genotoxic carcinogenesis with reference to specific examples of known non-genotoxic carcinogens.

An analysis of three vinyl chloride-induced DNA lesions epsilon-Ade, epsilon-Cyt and the imidazole lesion beta, reveals that beta- and epsilon-Cyt are equally mutagenic, whereas epsilon-Ade is the least mutagenic. All three lesions have different mutagenic specificities. Analysis of phage transferred DNA-containing lesions reveals that beta is the most genotoxic of the three DNA lesions due to the lack of purine and pyrimidine structures in beta. Epsilon-Cyt's toxicity is more than double that of epsilon-Ade's.

Identical classifications of RTX-toxins of Actinobacillus pleuropneumoniae and their genes were proposed after studying three diverse pore-forming RTX-toxins of this organism. The RTX-toxin derived from the reference strains for serotypes 1, 5a, 5b, 9, 10 and 11 were termed Apxl. This protein was found to be highly haemolytic and reveals increased cytotoxic activity toward pig alveolar macrophages and neutrophils, and has a molecular mass between 105 and 110kDa.

The synthesis of the 3-amino-1,4-dimethyl and 3-amino-1-methyl derivatives of 5H-pyrido(4,3-b)indole (Trp-P-1 and Trp-P-2) proceeds through the thermal electrocyclic reaction of the 1-azahexa-1,3,5-triene system involving the indole (b) bond. N-(benzenesulfonyl)indole provides the 2-vinylindole substrates via a four-step sequence. Trp-P-1 and Trp-P-2 are genotoxic heterocyclic amines produced by the overcooking of protein-containing food.

The L-type Ca2+ channels found in smooth and cardiac muscles contain receptor sites susceptible to either dihydropyridine or phenylalkylamine modulation. These binding sites promote high conservation in the Ca2+ channel alpha1 subunits involving Ca2+ channel antagonist reactions resulting in therapeutic effects. Moreover, results indicate that phenylalkylamine hinders Ca2+ ion movement via pore-blocking while dihydropyridine functions via extracellular gating alterations.

Several non-genotoxic carcinogens such as peroxisome proliferators and dioxins promote alterations in gene expression via the activation of intracellular receptor signal transduction pathways. These carcinogens imitate the function of receptor-specific natural ligands which facilitate cellular growth and eventually cause tumor formation. Experiments further indicate that hyperplasia is involved in the mitogenicity of the carcinogens. In addition, these carcinogens primarily interact with receptors included in the superfamily of steroid hormone receptors.

The development of experimental toxicology underwent three stages in the course of eight decades of biological and chemical research. The first stage began during the 1920s and included the identification of the lethality of various chemicals and the formation of different experimental techniques. The next stage comprised the investigation of the origin of toxic reactions which caused the incorporation of biomechanics in the practice of toxicology. The third and final stage, which endured from the 1970s to the present, involved extensive application of genetics in the assessment of toxicological responses resulting in more individualized examinations.

The use of a solid-phase cytometer was described to detect and enumerate the toxic alga Prymnesium parvum in natural samples, using a specific monoclonal antibody and indirect immunofluorescence. It was observed that solid-phase cytometer could be used to rapidly enumerate natural P. parvum cells and detection of other toxic algae, with an appropriate antibody or DNA probe.

The sensitivity of individual SOS promoters toward genotoxic substances is evaluated using four different green fluorescent protein (GFP)-based whole-cell biosensors. A new SOS-GFP whole-cell biosensor which is not only able to detect minute levels of genotoxins, but due to its use of the green fluorescent protein, also a reporter system which should be applicable in high-throughout screening as well as a wide variety of in situ detection studies is presented.

The genetic structures of the three described species of digenean trematodes such as Deropegus aspina, Nanophyetus salmincola and Plagioporus shawi that infect wild populations of salmonoid fishes in the Pacific Northwest of the United States are presented. The study demonstrates that variation in life cycles could predispose parasites to different genetic structures, thereby affecting the evolutionary potential of those parasites.

Results show that the two separate signaling pathways, SUMO-1 modification and ATM activation are induced by genotoxic stress. Data suggest that the two pathways work in unison and cause nuclear targeting and ubiquitylation of free NEMO, to facilitate the transcription factor NF-kappa B survival pathway.

Results reveal that in the transfected Escherichia coli with the single-stranded DNA genomes containing the lesions guanidinohydantoin and spiroiminodihydantoin of 7,8-dihydro-8-0x0-2'-deoxyguanine, the gunidinohydantoin lesion is bypassed as efficiently as the parent but with a mutagenic effect. The spiroiminohydantoin isomers strongly block DNA polymerase. Both cause nucleotide transversions stronger than the parent 7,8-dihydro-8-0x0-2'-deoxyguanine.

Research has been conducted on DNA damage distribution in hamster ovary cells exposed to UVA radiation. The authors describe the use of various techniques in investiggating this distribution, and they report that pyrimidine dimerization products are responsible for UVA-induced DNA damage in mammalian cells.

Results reveal that trans-4-Hydroxy-2-nonenal (4-HNE)-deoxyguanosine (dG) adducts are mutagenic and genotoxic in human cells and induce G-C and T-A transversions. Data further indicate that induction of genotoxicity and mutagenicity by 4-HNE-dG adducts in nucleotide excision repair (NER)-deficient human and Escherichia coli cells that in NER-proficient cells, suggesting that repairing of 4-HNE-dG adducts is mediated by NER pathway.