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Direct electrical stimulation has been used for decades as a gold standard clinical tool to map cognitive function in neurosurgery patients 1-8 . However, the molecular impact of electrical stimulation in the human brain is unknown. Here, using state-of-the-art transcriptomic and epigenomic sequencing techniques, we define the molecular changes in bulk tissue and at the single-cell level in the human cerebral cortex following direct electrical stimulation of the anterior temporal lobe in patients undergoing neurosurgery. Direct electrical stimulation surprisingly had a robust and consistent impact on the expression of genes related to microglia-specific cytokine activity, an effect that was replicated in mice. Using a newly developed deep learning computational tool, we further demonstrate cell type-specific molecular activation, which underscores the effects of electrical stimulation on gene expression in microglia. Taken together, this work challenges the notion that the immediate impact of electrical stimulation commonly used in the clinic has a primary effect on neuronal gene expression and reveals that microglia robustly respond to electrical stimulation, thus enabling these non-neuronal cells to sculpt and shape the activity of neuronal circuits in the human brain., Competing Interests: Competing interests T.A. is a scientific advisor to Aditum Bio and Radius Health and serves on the scientific advisory board of Embark Neuro. The other authors declare no conflicting interests.

The human brain extracts meaning using an extensive neural system for semantic knowledge. Whether broadly distributed systems depend on or can compensate after losing a highly interconnected hub is controversial. We report intracranial recordings from two patients during a speech prediction task, obtained minutes before and after neurosurgical treatment requiring disconnection of the left anterior temporal lobe (ATL), a candidate semantic knowledge hub. Informed by modern diaschisis and predictive coding frameworks, we tested hypotheses ranging from solely neural network disruption to complete compensation by the indirectly affected language-related and speech-processing sites. Immediately after ATL disconnection, we observed neurophysiological alterations in the recorded frontal and auditory sites, providing direct evidence for the importance of the ATL as a semantic hub. We also obtained evidence for rapid, albeit incomplete, attempts at neural network compensation, with neural impact largely in the forms stipulated by the predictive coding framework, in specificity, and the modern diaschisis framework, more generally. The overall results validate these frameworks and reveal an immediate impact and capability of the human brain to adjust after losing a brain hub., (© 2023. Springer Nature Limited.)

Here we report the morpho-functional features of a novel type of deep-layer neuron. The neuron was selected from a large pool of intracellularly labelled cells based on the large cell body, numerous spine-free dendrites with an overall interneuron morphology. However, the axon gave off long-range axons up to 2.8 mm from the parent soma in layers 5/6 before entering the white matter. The boutons were uniformly distributed along the axon without forming distinct clusters. Dendritic length, surface area and volume values were at least 3 times larger than any known cortical neuron types with the exception of giant pyramidal cells of layer 5. Electron microscopy of the boutons revealed that they targeted dendritic spines (78%) and less frequently dendritic shafts (22%). Nearly half of the postsynaptic dendrites were immunopositive to GABA. Superimposing the axonal field on the orientation map obtained with optical imaging showed a preponderance of boutons to cross-orientations (38%) and an equal representation of iso- and oblique orientations (31%). The results suggest an integrating role for the layer 6 stellate neuron which projects to a functionally broad range of neurons in the deep cortical layers and to other cortical and/or subcortical regions., (© 2022. The Author(s).)

The mirror technique adapted for electron microscopy allows correlating neuronal structures across the cutting plane of adjoining light microscopic sections which, however, have a limited thickness, typically less than 100 µm (Talapka et al. in Front Neuroanat, 2021, https://doi.org/10.3389/fnana.2021.652422 ). Here, we extend the mirror technique for tissue blocks in the millimeter range and demonstrate compatibility with serial block-face electron microscopy (SBEM). An essential step of the methodological improvement regards the recognition that unbound resin must be removed from the tissue surface to gain visibility of surface structures. To this, the tissue block was placed on absorbent paper during the curing process. In this way, neuronal cell bodies could be unequivocally identified using epi-illumination and confocal microscopy. Thus, the layout of cell bodies which were cut by the sectioning plane can be correlated with the layout of their complementary part in the adjoining section processed for immunohistochemistry. The modified mirror technique obviates the spatial limit in investigating synaptology of neurochemically identified structures such as neuronal processes, dendrites and axons., (© 2022. The Author(s).)

In the nervous system synaptic input arrives chiefly on dendrites and their type and distribution have been assumed pivotal in signal integration. We have developed an immunohistochemistry (IH)-correlated electron microscopy (EM) method - the "mirror" technique - by which synaptic input to entire dendrites of neurochemically identified interneurons (INs) can be mapped due preserving high-fidelity tissue ultrastructure. Hence, this approach allows quantitative assessment of morphometric parameters of synaptic inputs along the whole length of dendrites originating from the parent soma. The method exploits the fact that adjoining sections have truncated or cut cell bodies which appear on the common surfaces in a mirror fashion. In one of the sections the histochemical marker of the GABAergic subtype, calbindin was revealed in cell bodies whereas in the other section the remaining part of the very same cell bodies were subjected to serial section EM to trace and reconstruct the synaptology of entire dendrites. Here, we provide exemplary data on the synaptic coverage of two dendrites belonging to the same calbindin-D 28 K immunopositive IN and determine the spatial distribution of asymmetric and symmetric synapses, surface area and volume of the presynaptic boutons, morphometric parameters of synaptic vesicles, and area extent of the active zones., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Talapka, Kocsis, Marsi, Szarvas and Kisvárday.)

Human brain pathways supporting language and declarative memory are thought to have differentiated substantially during evolution. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed functional imaging to visualize the effects of direct electrical brain stimulation in macaque monkeys and human neurosurgery patients. We discovered comparable effective connectivity between caudal auditory cortex and both ventro-lateral prefrontal cortex (VLPFC, including area 44) and parahippocampal cortex in both species. Human-specific differences were clearest in the form of stronger hemispheric lateralization effects. In humans, electrical tractography revealed remarkably rapid evoked potentials in VLPFC following auditory cortex stimulation and speech sounds drove VLPFC, consistent with prior evidence in monkeys of direct auditory cortex projections to homologous vocalization-responsive regions. The results identify a common effective connectivity signature in human and nonhuman primates, which from auditory cortex appears equally direct to VLPFC and indirect to the hippocampus. VIDEO ABSTRACT., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To assess chromogranin A (CGA) and neuron-specific enolase (NSE) levels and changes in these at different stages of prostatic adenocarcinoma (PCA)., Methods: Overall, 1095 serum samples from 395 patients, divided into three treatment groups, were analysed; the radical prostatectomy (RP) cohort (n = 157) included patients with clinically localized PCA, while the docetaxel (DOC) and the abiraterone (ABI)/enzalutamide (ENZA) cohorts included 95 and 143 patients, respectively, with metastatic castration-resistant prostate cancer. CGA, NSE and total PSA levels were measured using the KRYPTOR method., Results: Baseline CGA and NSE levels were higher in castration-resistant (DOC and ABI/ENZA cohorts) than in hormone-naïve, clinically localized PCA (P < 0.001). High baseline CGA levels were independently associated with poor overall survival in both the DOC and the ABI/ENZA cohorts, with a stronger association in the ABI/ENZA cohort. In the ABI/ENZA cohort, a > 50% CGA increase at 3 months was associated with poor survival, especially in patients with high baseline CGA levels., Conclusions: The two- to threefold higher neuroendocrine marker levels in castration-resistant compared to hormone-naïve PCA support the presence of neuroendocrine transdifferentiation under androgen deprivation therapy. Our results showed patients with high baseline CGA levels who experienced a further CGA increase during ABI and ENZA treatment had the poorest prognosis. Serum CGA levels could help in tailoring and monitoring therapy in advanced PCA., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

The dynamics of perceptual bistability, the phenomenon in which perception switches between different interpretations of an unchanging stimulus, are characterised by very similar properties across a wide range of qualitatively different paradigms. This suggests that perceptual switching may be triggered by some common source. However, it is also possible that perceptual switching may arise from a distributed system, whose components vary according to the specifics of the perceptual experiences involved. Here we used a visual and an auditory task to determine whether individuals show cross-modal commonalities in perceptual switching. We found that individual perceptual switching rates were significantly correlated across modalities. We then asked whether perceptual switching arises from some central (modality-) task-independent process or from a more distributed task-specific system. We found that a log-normal distribution best explained the distribution of perceptual phases in both modalities, suggestive of a combined set of independent processes causing perceptual switching. Modality- and/or task-dependent differences in these distributions, and lack of correlation with the modality-independent central factors tested (ego-resiliency, creativity, and executive function), also point towards perceptual switching arising from a distributed system of similar but independent processes.

In everyday acoustic scenes, figure-ground segregation typically requires one to group together sound elements over both time and frequency. Electroencephalogram was recorded while listeners detected repeating tonal complexes composed of a random set of pure tones within stimuli consisting of randomly varying tonal elements. The repeating pattern was perceived as a figure over the randomly changing background. It was found that detection performance improved both as the number of pure tones making up each repeated complex (figure coherence) increased, and as the number of repeated complexes (duration) increased - i.e., detection was easier when either the spectral or temporal structure of the figure was enhanced. Figure detection was accompanied by the elicitation of the object related negativity (ORN) and the P400 event-related potentials (ERPs), which have been previously shown to be evoked by the presence of two concurrent sounds. Both ERP components had generators within and outside of auditory cortex. The amplitudes of the ORN and the P400 increased with both figure coherence and figure duration. However, only the P400 amplitude correlated with detection performance. These results suggest that 1) the ORN and P400 reflect processes involved in detecting the emergence of a new auditory object in the presence of other concurrent auditory objects; 2) the ORN corresponds to the likelihood of the presence of two or more concurrent sound objects, whereas the P400 reflects the perceptual recognition of the presence of multiple auditory objects and/or preparation for reporting the detection of a target object., (Copyright © 2016. Published by Elsevier Inc.)

The auditory environment typically comprises several simultaneously active sound sources. In contrast to the perceptual segregation of two concurrent sounds, the perception of three simultaneous sound objects has not yet been studied systematically. We conducted two experiments in which participants were presented with complex sounds containing sound segregation cues (mistuning, onset asynchrony, differences in frequency or amplitude modulation or in sound location), which were set up to promote the perceptual organization of the tonal elements into one, two, or three concurrent sounds. In Experiment 1, listeners indicated whether they heard one, two, or three concurrent sounds. In Experiment 2, participants watched a silent subtitled movie while EEG was recorded to extract the object-related negativity (ORN) component of the event-related potential. Listeners predominantly reported hearing two sounds when the segregation promoting manipulations were applied to the same tonal element. When two different tonal elements received manipulations promoting them to be heard as separate auditory objects, participants reported hearing two and three concurrent sounds objects with equal probability. The ORN was elicited in most conditions; sounds that included the amplitude- or the frequency-modulation cue generated the smallest ORN amplitudes. Manipulating two different tonal elements yielded numerically and often significantly smaller ORNs than the sum of the ORNs elicited when the same cues were applied on a single tonal element. These results suggest that ORN reflects the presence of multiple concurrent sounds, but not their number. The ORN results are compatible with the horse-race principle of combining different cues of concurrent sound segregation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The ability to isolate a single sound source among concurrent sources is crucial for veridical auditory perception. The present study investigated the event-related oscillations evoked by complex tones, which could be perceived as a single sound and tonal complexes with cues promoting the perception of two concurrent sounds by inharmonicity, onset asynchrony, and/or perceived source location difference of the components tones. In separate task conditions, participants performed a visual change detection task (visual control), watched a silent movie (passive listening) or reported for each tone whether they perceived one or two concurrent sounds (active listening). In two time windows, the amplitude of theta oscillation was modulated by the presence vs. absence of the cues: 60-350ms/6-8Hz (early) and 350-450ms/4-8Hz (late). The early response appeared both in the passive and the active listening conditions; it did not closely match the task performance; and it had a fronto-central scalp distribution. The late response was only elicited in the active listening condition; it closely matched the task performance; and it had a centro-parietal scalp distribution. The neural processes reflected by these responses are probably involved in the processing of concurrent sound segregation cues, in sound categorization, and response preparation and monitoring. The current results are compatible with the notion that theta oscillations mediate some of the processes involved in concurrent sound segregation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In two experiments, we assessed the effects of combining different cues of concurrent sound segregation on the object-related negativity (ORN) and the P400 event-related potential components. Participants were presented with sequences of complex tones, half of which contained some manipulation: one or two harmonic partials were mistuned, delayed, or presented from a different location than the rest. In separate conditions, one, two, or three of these manipulations were combined. Participants watched a silent movie (passive listening) or reported after each tone whether they perceived one or two concurrent sounds (active listening). ORN was found in almost all conditions except for location difference alone during passive listening. Combining several cues or manipulating more than one partial consistently led to sub-additive effects on the ORN amplitude. These results support the view that ORN reflects a combined, feature-unspecific assessment of the auditory system regarding the contribution of two sources to the incoming sound., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The ability of the auditory system to parse complex scenes into component objects in order to extract information from the environment is very robust, yet the processing principles underlying this ability are still not well understood. This study was designed to investigate the proposal that the auditory system constructs multiple interpretations of the acoustic scene in parallel, based on the finding that when listening to a long repetitive sequence listeners report switching between different perceptual organizations. Using the "ABA-" auditory streaming paradigm we trained listeners until they could reliably recognize all possible embedded patterns of length four which could in principle be extracted from the sequence, and in a series of test sessions investigated their spontaneous reports of those patterns. With the training allowing them to identify and mark a wider variety of possible patterns, participants spontaneously reported many more patterns than the ones traditionally assumed (Integrated vs. Segregated). Despite receiving consistent training and despite the apparent randomness of perceptual switching, we found individual switching patterns were idiosyncratic; i.e., the perceptual switching patterns of each participant were more similar to their own switching patterns in different sessions than to those of other participants. These individual differences were found to be preserved even between test sessions held a year after the initial experiment. Our results support the idea that the auditory system attempts to extract an exhaustive set of embedded patterns which can be used to generate expectations of future events and which by competing for dominance give rise to (changing) perceptual awareness, with the characteristics of pattern discovery and perceptual competition having a strong idiosyncratic component. Perceptual multistability thus provides a means for characterizing both general mechanisms and individual differences in human perception.

Natural killer (NK) cells host in the human endometrium with dedicated role in reproductive physiology. Interestingly, malignant transformation of these specialized cells has not been presented thus far. Here we report a primary endometrial NK-cell lymphoma of a 48 year-old patient presenting with irregular bleeding. The endometrial curetting showed a dense lymphomatous infiltrate demonstrating highly infiltrative aggressive features with characteristic angiocentric, partially angiodestructive growth pattern and accompanying focal necroses. The lymphoma cells displayed a CD3ε/CD56/TIA-1/granzyme-B-positive and CD5/CD4/CD8/TCRγδ-negative immunophenotype, proved to be positive for Epstein-Barr virus by EBER in situ hybridization, and revealed no clonal T-cell receptor gene rearrangement. The diagnosis of uterine extranodal NK-cell lymphoma, nasal-type was made. Clinically, the disease was limited to the uterus at diagnosis, but progressed rapidly, and the patient died within 5 months due disseminated lymphoma, irrespective of intensive chemotherapy. Genuine NK-cell lymphomas occurring in the uterus as primary site seem to be rare making the therapeutic decisions extremely complicated.

A non-transformed (Vero) and two tumor cell lines (HepG2 and MCF-7) were treated with 10nM to 100 microM formaldehyde. Lower doses (10nM to 10 microM) enhanced the viability of the cultured cells, measured by MTT assay. Higher doses (75-100 microM) decreased viability of the cells by 50% or more. The 100 microM concentration of HCHO has been chosen for combination treatment of the three cell lines with a series of concentrations (0.2-100 microM) of resveratrol, a phytoestrogen occurring in various fruits. Resveratrol decreased the cytotoxicity of formaldehyde depending on cell line and point of time, especially in case of MCF-7 cells at 24 and 72 h, Vero cells at 24h and HepG2 cells at 48 h after treatment. Possible modes of interactions are discussed, considering the role of resveratrol in formaldehyde metabolism and also the estrogen receptor positivity of MCF-7 cells.

Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonasel (PON1) and arylesterase activities, and lipid-profile in 37 SLE patients and 30 age-/sex-matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti-oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, SLEDAI 2 (0-15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured antioxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 +/- 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 +/- 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL-C, HDL-C, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti-PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL-subfractions or enzyme abnormalities in HDL remodeling.

Systemic lupus erythematosus is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Objectives were to determine endothelial dysfunction with a non-invasive method in lupus patients and to analyse correlation with risk factors and atherosclerotic complications. Sixty-one SLE patients and 26 healthy age- and sex-matched control subjects were entered into the study. The diameters of brachial artery at rest, during reactive hyperaemia, and after glyceril trinitrate administration, as well as the intima-media thickness of the common carotid artery were measured using high-resolution B-mode ultrasonography. Demographic characteristics, lipid profile, paraoxonase activity, concentration of anti-phospholipid antibodies and anti-oxLDL were assessed together with atherosclerotic complications. The endothelium dependent vasodilation (FMD) was significantly impaired in SLE patients as compared to controls. The absolute difference of vessel diameter (Deltad) was 0.25+/-0.15 mm vs. 0.38+/-0.16 mm (p=0.001), and Deltad as in percent of the rest diameter was 7.31+/-5.2% vs. 9.86+/-3.87% (p=0.013) in lupus patients and controls, respectively. Nitrate mediated dilation (NMD) did not differ. FMD negatively correlated with age, systolic and diastolic blood pressure in SLE, but did not show significant correlation with the other examined parameters. However, FMD significantly differed between SLE patients with (5.54+/-4.36%) and without (8.81+/-5.28%) cardiovascular complications (p=0.01). The determination of flow-mediated vasodilation is a useful method to detect endothelial dysfunction in lupus patients, as reduced capacity of brachial artery may distinguish between SLE patients and healthy subjects, as well as lupus patients with and without atherosclerotic vascular complications.

The beneficial effect of trans-resveratrol (RESV) on health is well documented. Our aim was to study the putative preventive effect of RESV on the cytotoxicity of frequently used herbicides (alachlor, acetochlor). Estrogen receptor positive (ER+) MCF-7 human mammary carcinoma, HepG2 (ER+) human hepatocellular carcinoma and VERO estrogen receptor negative (ER-) non-transformed monkey fibroblast cell lines were treated with alachlor and acetochlor (2-500 microg/ml) as toxic agents, and RESV (10 microM) as preventive agent. The MTT dye reduction assay was performed to test cytotoxicity, and flow cytometry to test cell proliferation and apoptosis. RESV is not cytotoxic in the concentration range of 1-100 microM on neither cell lines examined after 24 h, but cytotoxic on Vero and MCF-7 cells at 100 microM after 48h, and on all three cell lines after 72 h. On both ER+ cell lines a stimulation of viability occurs in the low concentration range (0.5-12.5 microM) as detected by the MTT assay. Cell cycle analysis of the culture shows a significant increase of S-phase cells at low concentrations of RESV (10-50 microM) and a decrease in the 100-200 microM concentration range. The ratio of apoptotic cells significantly increases after the administration of 50 microM RESV, depending on the incubation time. The cytotoxicity of 20-65 microg/ml alachlor and 10-65 microg/ml acetochlor was significantly decreased by the addition of 10 microM RESV in Vero ER- cells whereas no significant change was detected on ER+ cell lines MCF-7 and HepG2. These results show that RESV protects non-transformed ER- cells, but has no such effect on ER+ tumor cells.

Avemar, a fermented wheat germ extract, has been applied in the supplementary therapy of human cancers. Because tamoxifen is commonly used in the therapy of ER+ breast cancer, in this study the combined effect of tamoxifen and Avemar treatment was investigated on MCF-7 breast cancer cells, in order to detect a possible agonistic or antagonistic action. Cytotoxicity was measured by MTT assay, the percentage of mitoses and apoptotic cells was determined morphologically, apoptosis and S-phase was measured by flow cytometry, and estrogen-receptor activity was determined by semiquantitative measurement of the estrogen-responsive pS2 gene mRNA production. Tamoxifen (1 nM) alone had no effect on the percentage of the apoptotic cell fraction and significantly reduced the percentage of the S-phase, compared to untreated cells. Avemar (625 microg/mL) significantly increased apoptosis after 48 hours of treatment. Tamoxifen together with Avemar significantly increased apoptosis already 24 hours after starting treatment but had only a slight (not significant) effect on mitosis and S-phase. Estrogen-receptor activity of MCF-7 cells was enhanced by Avemar, decreased by tamoxifen, and was further decreased by combined tamoxifen and Avemar treatment. As apoptosis increased when Avemar was added to tamoxifen treatment, the use of supplementary therapy with Avemar in the case of ER+ breast tumors may enhance the therapeutic effects of tamoxifen.

Avemar (Biromedicina Co., Budapest, Hungary), a wheat germ preparation with immunomodulant and antimetastatic activity, was applied simultaneously with cytostatic drugs of different modes of action, in vitro and in vivo, in order to find out whether this simultaneous administration exerts an antagonistic or a synergistic effect on the viability of cell cultures, tumor growth, and survival of animals, inoculated with a transplantable mouse tumor (3LL-HH). In vitro, Avemar did not influence the effect on the viability of MCF-7, HepG2, or Vero cells, exerted by Dacarbazine, 5-fluorouracyl, or Adriblastina. In vivo, Avemar, combined with Endoxan, Navelbine, and doxorubicin, did not prevent the tumor growth inhibitory effect of the cytostatic drugs. The combination of Avemar with the cytostatic drugs did not increase the toxicity of the cytostatic compounds, and did not exert any toxic effect. Avemar may be administered together with cytostatic drugs, without the risk of increasing toxicity or decreasing antiproliferative activity.

Patients with prosthetic valves were investigated by Doppler echocardiography in 902 cases between November 1987 and February 1990. The parameters of 209 of 344 mitral and 258 of 299 aortic prosthetic valves were evaluated. No significant correlation was found between the type of aortic or mitral prosthetic valves and the measured gradient. As concerns the size of the valve and the measured gradient, a close correlation for aortic valve replacement was detected. For a normally functioning mitral prosthetic valve, a maximum early diastolic velocity of less than 2 m/s (16 mm Hg gradient) and a pressure half-time of less than 130 ms (mitral valve area 1.8 cm2) were characteristic. In cases of aortic valve replacements, the maximum velocity was less than 3 m/s (36 mm Hg gradient), except for the small-diameter valves. More than 95% of the cases met these criteria. (Even if small-diameter valves were included, a maximum velocity of more than 3 m/s occurred only in 8.9%.) Doppler echocardiography is a suitable tool for detecting normal prosthetic valve function, while colour Doppler allows the optimal alignment of jet direction and Doppler beam.

Three thiocarbamate herbicides, butylate (S-ethyl-diisobutylthiocarbamate), vernolate (S-propyl dipropylthiocarbamate) and molinate (S-ethyl-N,N-hexamethylenethiocarbamate) were assayed for cytogenetic effect in the mouse bone marrow micronucleus test. Butylate was inactive in bone marrow, vernolate caused a marginal increase in the incidence of micronucleated polychromatic erythrocytes only at a high toxic dose level. Molinate, the N,N-hexamethylene derivative was, however, strongly active in the bone marrow, causing a high frequency of micronucleated erythrocytes, even at subtoxic concentrations.

In Fischer F344/LATI rats of both sexes the herbicide atrazine was given in the diet at concentrations of 0, 375 and 750 ppm for 126 weeks. Food and water consumption was similar in the treated and control groups. Feeding of atrazine resulted in dose-dependent depression of body weight gain in both sexes. There was no difference in the survival among the females. The males in the treated groups lived significantly longer than the controls. Exposure to atrazine resulted in significantly increased incidence of mammary tumors in the high dose male group. Uterine carcinomas were observed at a dose-related, significantly increased incidence. The number of combined leukemias/lymphomas increased in the treated males and females, but it was statistically significant only for females. The total number of malignant tumors showed a dose-related increase in both sexes. Other tumors and nontumorous lesions occurred at background level and were not influenced by treatment.