Showing papers in "Mutation Research\/genetic Toxicology in 1982"
TL;DR: Commercial and technical grades of 10 insecticides were evaluated for genotoxicity with Salmonella typhimurium and Saccharomyces cerevisiae directly and following plant and animal activation.
Abstract: Commercial and technical grades of 11 herbicides and 13 combinations of commercial grade herbicides were evaluated for their genotoxic properties with Salmonella typhimurium, Saccharomyces cerevisiae directly and following plant and animal activation, or with Zea mays. The herbicides were related by their use in commercial corn (maize) production. Commercial grade formulations of each herbicide and combination of herbicides were also evaluated in situ with the pollen waxy locus assay of Z. mays. Eradicane and bifenox were negative in all assays. Alachlor, propachlor, procyazine and SD50093 (a formulation of cyanazine plus atrazine) were positive in one assay. Cyanazine, dicamba and metolachlor were positive in 2 assays. Atrazine, simazine and butylate were tested only in situ. Atrazine and simazine were positive and butylate was negative. Of the combinations of herbicides evaluated with the 3 genetic assays, alachlor plus bifenox and procyazine plus metolachlor were positive in 1 assay and metolachlor plus atrazine was positive in 2 assays. Of the combinations of herbicides evaluated only in situ, butylate plus atrazine, eradicane plus atrazine, eradicane plus cyanazine and metolachlor plus cyanazine were positive while butylate plus cyanazine was negative.
175 citations
TL;DR: Of the 9 chemicals tested after metabolic activation by liver microsomal S9 preparation, significant increases in SCE frequency were seen in diazinon-, dimethoate-, Dursban- and Phosdrin-treated cells.
Abstract: In the present study, cytotoxic, cytostatic and cytogenetic effects of a number of organophosphate pesticides on human lymphoid cells (LAZ-007) in culture have been examined. Cytotoxic effects were dose related and often led to extensive cell kill. The pronounced effects of various organophosphates on the cell-cycle traverse were shown in data based on the enumeration of M 1 and M 3 metaphases after incubation of cells with BrdU. In cells incubated with 20 μg/ml of the various chemicals, the number of M 1 metaphases ranged from 6% (R-1303) to 18% (Azodrin) compared to no M 1 metaphases in control cultures. The number of M 3 s in cultures treated with 20gmg/ml of the various chemicals tested varied from 0% (Phosdrin) to 7% (parathion) as compared to 17% in control cultures. 11 out of the 14 organophosphates tested, significantly increased the SCE frequency. Of the 9 chemicals tested after metabolic activation by liver microsomal S9 preparation, significant increases in SCE frequency were seen in diazinon-, dimethoate-, Dursban- and Phosdrin-treated cells.
137 citations
TL;DR: Dose-dependent increases in aneuploidy were seen at 10(-4) M and higher concentrations of both aldehydes, with incidences twice as high for MA as for AA.
Abstract: The genotoxic effects of malonaldehyde (MA) and acetaldehyde (AA) were investigated using primary cultures of rat skin fibroblasts Exposure to MA at 10−4 to 10−3 M concentrations resulted in dose-dependent production of micronuclei MA was approx 10 times as potent as AA with respect to micronuclei formation Treatment with 10−4 and 10−3 M concentrations of MA for 12 h produced chromosomal aberrations (chromosomal fragments, achromatic lesions and chromatid breaks) in 14 and 34% of metaphases, respectively At 24 h the corresponding frequencies were 46 and 52% AA at analogous concentrations produced aberrations in 4 and 14% of metaphases at 12 h, and 20 and 40% at 24 h Dose-dependent increases in aneuploidy were seen at 10−4 M and higher concentrations of both aldehydes, with incidences twice as high for MA as for AA
84 citations
TL;DR: Antioxidants in the diet may have a role in lowering the body's exposure to endogenously produced mutagens, and addition of ascorbic acid and α-tocopherol directly to feces led to no change in mutagenicity.
Abstract: The effect of supplemental ascorbic acid and α-tocopherol on fecal mutagenicity was examined in 2 studies involving 20 healthy human donors aged 22–55 years. The vitamins were given at a dose of 400 mg daily each. The mutagen was extracted from individual frozen feces samples with dichloromethane, and assayed with Salmonella typhimurium tester strain TA100 without microsomal activation. In the first study, with a single donor on a controlled diet, the fecal mutagenicity decreased (P < 0.001) on treatment to 21% of control. In the second study, with 19 donors on free-choice diets, the mutagenicity in producers on treatment decreased (P < 0.01) to 26% of control. Addition of ascorbic acid and α-tocopherol directly to feces led to no change in mutagenicity. Antioxidants in the diet may have a role in lowering the body's exposure to endogenously produced mutagens.
73 citations
TL;DR: Antioxidants and several other compounds, some of which are known to inhibit carcinogenicity, have been screened for their effectiveness as inhibitors of benzo[a]pyrene (BP) mutagenicity towards Salmonella typhimurium strain TA98 in the Ames test, finding that retinol, phenothiazine, disulfiram, phenethylisothiocyanate and phenylisothuyanate were the most effective inhibitors.
Abstract: Antioxidants and several other compounds, some of which are known to inhibit carcinogenicity, have been screened for their effectiveness as inhibitors of benzo[a]pyrene (BP) mutagenicity towards Salmonella typhimurium strain TA98 in the Ames test. A total of 32 compounds were tested. In the assay, metabolic activation of BP (8.2 nmoles/plate) was mediated by the S9 fraction from β-naphthoflavone-induced rat livers. Among compounds which are known to inhibit carcinogenicity, retinol, phenothiazine, disulfiram, phenethylisothiocyanate and phenylisothiocyanate were the most effective inhibitors of BP mutagenicity, being effective at equimolar concentrations. Several other compounds showed inhibition at higher concentrations of antioxidant and the remainder showed little or no inhibition. Dose-response curves have been obtained for the 17 most active compounds. No general pattern of inhibition is obvious from our studies, inhibitors are not drawn from any single class of compounds, nor does a particular compound necessarily appear to inhibit more than one mutagen.
70 citations
TL;DR: Fish could be a useful biological model for studying the teratogenic, carcinogenic and mutagenic effects of environmental chemicals as well as in vivo for the detection of potential mutagens.
Abstract: The possibilities were explored of using fish as a cytogenetic model in vivo for the detection of potential mutagens. Boleophthalmus dussumieri (2n = 46, fairly large acrocentric chromosomes), an edible mud-skipper and a widely occurring Goby along the Bombay coast, was chosen as the test species after screening 20 species of fish locally available. I.m. injections of mitomycin C in the dose range of 0.5-2.0 mg/kg body weight resulted in a significant increase in the frequency of aberrations per metaphase compared with the control. A dose-response effect was also evident. The types of aberration observed included chromatid and isochromatid breaks, fragments, rings, exchanges and unclassified markers. A significant increase in the number of gaps was also observed. Clastogenic effects of metals such as Hg, Se and Cr in the form of phenyl mercuric acetate, selenium dioxide and sodium dichromate following direct (i.m. injections) and indirect (dissolved in the aquarial water) exposures were studied. A marked enhancement was noticed in the aberration frequency at most of the dose levels tested. Spontaneous chromosomal aberrations in this species were rather rare and occurred at a rate close to zero. If developed along proper lines, fish could be a useful biological model for studying the teratogenic, carcinogenic and mutagenic effects of environmental chemicals.
61 citations
TL;DR: It is suggested that secondary direct-acting mutagens might be partly formed by the nitration of polycyclic aromatic hydrocarbons with NO2 in the atmosphere because concentrations of B[a]P, NO2 and NO-3 increased simultaneously when the highest direct- acting mutagenic activity was observed.
Abstract: The mutagenicity of airborne particles was studied in the Ames Salmonella system. The mutagenic activity of benzene extracts from airborne particles was more active in strain TA98 in the presence and absence of S9 mix than in strain TA100. The presence of mutagens, other than benzo[ a ]pyrene (B[ a ]P), which did not require S9 mix, was indicated. However, the monthly variation of direct-acting mutagenic activity showed a pattern similar to that of B[ a ]P at atmospheric concentration. The monthly variations of atmospheric NO, NO 2 , NO − 2 and NO − 3 concentrations were also similar to that of the direct-acting mutagenic activity. Atmospheric concentrations of heavy metals such as Pb, Zn, Cd, V and Cu were also found to be related to direct-acting mutagenic activity. These results suggest that emissions from automobiles, home heaters and power plants etc. may be a primary source of atmospheric, direct-acting mutagens. It is suggested that secondary direct-acting mutagens might be partly formed by the nitration of polycyclic aromatic hydrocarbons (PAH) with NO 2 in the atmosphere because concentrations of B[ a ]P, NO 2 and NO − 3 increased simultaneously when the highest direct-acting mutagenic activity was observed.
59 citations
TL;DR: The clastogenic activity of MEHP suggests a role for this compound in the observed carcinogenicity of DEHP and its positive effect in the dominant lethal assay.
Abstract: The widely used plasticizer di(2-ethylhexyl)phthalate (DEHP), its hydrolysis products mono(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol, and also phthalic acid have been tested for clastogenic activity in cultured Chinese hamster ovary (CHO) cells. Only MEHP was found to cause chromosome damage. MEHP was without effect in the SCE and HGPRT mutation test in CHO cells. The clastogenicity of MEHP suggest a role for this compound in the observed carcinogenicity of DEHP and its positive effect in the dominant lethal assay.
55 citations
TL;DR: The reason for lack of evident cytogenetic damage in primary cells may lie in the greater spontaneous karyotype instability of transformed (permanent) cell lines or may be connected with the less efficient DNA repair capacity of Chinese hamster ovary cells.
Abstract: Asbestos and fine glass fibre, which induce high levels of chromosome aberrations and polyploidy in Chinese hamster permanent cell lines, were found to cause no increase in chromosome damage or polyploidy in primary human fibroblasts or in human lymphoblastoid lines. In common with permanent cell lines of hamster or human origin, treatment of primary human fibroblasts with higher doses of asbestos or fine glass resulted in almost total growth inhibition, showing that the primary cells are not unaffected by these agents. The reason for lack of evident cytogenetic damage in primary cells may lie in the greater spontaneous karyotype instability of transformed (permanent) cell lines or may be connected with the less efficient DNA repair capacity of Chinese hamster ovary cells.
52 citations
TL;DR: There was no significant increase of sister-chromatid exchange (SCEs) in smoking PCP workers, as compared with smoking controls, and within the control group, smokers had a higher incidence of SCEs than non-smokers.
Abstract: Chromosome analyses were carried out on peripheral lymphocytes from 22 male workers employed at a pentachlorophenol (PCP) producing factory. As compared with a group of 22 matched controls as a small, but significant, increase in the frequency of dicentrics and acentrics was observed. There was no significant increase of sister-chromatid exchanges (SCEs) in smoking PCP workers, as compared with smoking controls. Within the control group, smokers had a higher incidence of SCEs than non-smokers.
50 citations
TL;DR: The number of SCEs was significantly increased in smoking and non-smoking toluene-exposed workers compared with the corresponding control groups, and significantly higher yields of chromatid breaks, Chromatid exchanges and gaps were observed.
Abstract: Cytogenetic analyses were carried out in peripheral lymphocytes from 20 male workers exposed only to toluene in a rotogravure plant for more than 16 years As compared with a group of 24 unexposed controls, significantly higher yields of chromatid breaks, chromatid exchanges and gaps were observed The number of SCEs was significantly increased in smoking and non-smoking toluene-exposed workers compared with the corresponding control groups
TL;DR: Of 12 tobacco constituents tested, none showed mutagenic activity in the Ames test, and the substances pyrrolidine, nicotine, anatabine, myosmine, 2,3′-dipyridyle and nicotyrine induced repairable DNA damage in a test with Escherichia coli.
Abstract: Of 12 tobacco constituents tested, none showed mutagenic activity in the Ames test. The substances pyrrolidine, nicotine, anatabine, myosmine, 2,3′-dipyridyle and nicotyrine induced repairable DNA damage in a test with Escherichia coli pol A + / pol A − .
TL;DR: A suitable protocol for routine application of the 2 bone-marrow tests is discussed in view of the guidelines presently under preparation in the EEC and the OECD and against a sub-acute treatment regimen and for a single treatment regimen with multiple sampling intervals.
Abstract: The cytogenetic effects, in vivo, of the polycyclic hydrocarbon benzo[a]pyrene were studied in adult male mice by chromosome analysis and the micronucleus test. To establish the appropriate time for bone-marrow sampling, the interval between treatment and preparation was varied. The maximal response in the micronucleus test was found 36 h after treatment versus 30 h when chromosomal aberrations were analyzed. In the micronucleus test the lowest effective dose was 25 mg/kg, whereas a significant effect (P less than 0.001) was observed at 6.25 mg/kg when aberrations were used as the mutagenic end-point. The results show that, with single treatments and different sampling intervals applied in both tests, aberration analysis had a higher resolving power than the micronucleus test at the time of maximal response. A suitable protocol for routine application of the 2 bone-marrow tests is discussed in view of the guidelines presently under preparation in the EEC and the OECD. Arguments are presented against a sub-acute treatment regimen and for a single treatment regimen with multiple sampling intervals.
TL;DR: The induction of micronuclei in mouse bone marrow by the organophosphorus insecticide gardona caused toxicity of marrow indicated as significant increases in the percentage of polychromatic erythrocytes over that of the control.
Abstract: The induction of micronuclei in mouse bone marrow by the organophosphorus insecticide gardona (also known as tetrachlorvinphos) was tested. 3 routes of administration were used for the pure insecticide: intraperitoneal, oral and dermal. The different routes of treatment with gardona caused toxicity of marrow indicated as significant increases in the percentage of polychromatic erythrocytes over that of the control. Intraperitoneal and oral treatments induced a statistically significant percentage of micronucleated PE.
TL;DR: 4 chlorinated biphenyl and 5 chlorinated dibenzofuran compounds have been evaluated in the reversion assay developed by B.N Ames using Salmonella typhimurium histidine auxotrophs and were nonmutagenic for strains TA98 and TA100 when tested over a 3-log dose range.
Abstract: 4 chlorinated biphenyl and 5 chlorinated dibenzofuran compounds have been evaluated in the reversion assay developed by B.N. Ames using Salmonella typhimurium histidine auxotrophs. All these compounds (2,4,2′,4′-tetrachlorobiphenyl, 3,4,3′,4′-tetrachlorobiphenyl, 4-chlorobiphenyl, 2,4,6,2′,4′,6′-hexachlorobiphenyl, dibenzofuran, 2,9-dichlorodibenzofuran, 3,6-dichlorodibenzofuran, 2,3,7,8-tetrachlorodibenzofuran and octachlorodibenzofuran) were nonmutagenic for strains TA98 and TA100 when tested over a 3-log dose range. They were also not mutagenic whether or not varying concentrations of microsomal extracts (S9) from uninduced rats or from rats induced by several methods were included in the experimental protocol.
TL;DR: Specimens of large fungi (mushrooms) were screened for mutagenic activity by the Salmonella/microsome assay, with strains TA98, TA2637 and TA100 exhibiting a significant but for the most part weak activity.
Abstract: Specimens of large fungi (mushrooms) were screened for mutagenic activity by the Salmonella/microsome assay, with strains TA98, TA2637 and TA100. Out of 48 species tested, 37 exhibited a significant but for the most part weak activity. The activity observed in the presence of S9 mix was typically between 0 and 50% of that without, and in no case was the activity increased in the presence of microsomal enzymes. Six metabolites reported to occur in some of the species included in this investigation were also tested. Significant mutagenic activity was found with isovelleral (5) from Lactarius sp., agaritine (3) from Agaricus bisporus and related sp. and β-nitraminoalanine (7) from Agaricus silvaticus. Isovelleral may be a major mutagen in some of the sharp-tasting and mutagenic Russulaceae sp. A. bisporus (cultivated specimen) was weakly mutagenic toward all three strains of S. typhimurium used, and agaritine was weakly active toward TA2637 alone. This implies that this fungus might contain other mutagenic material as well. β-Nitraminoalanine was not found in the particular collection of A. silvaticus tested here. The mutagenicity observed for the fungus in this work may therefore be due to other metabolites. Even though many species found to be mutagenic are used as food, it seems premature to make specific recommendations about eventual health risks. Further information is needed about the chemistry and toxicology of the active compounds as well as about the effects of various methods used in preparing mushrooms for food.
TL;DR: An examination of the effect of the metabolizing system's concentration on mutagenicity showed that quinoline, benzo[f]quinoline, and phenanthridine have different optima.
Abstract: Several unsubstituted aza-arenes have been found to be more mutagenic to Salmonella typhimurium than their corresponding parent hydrocarbons. In most cases, the activity of these compounds depended on the presence of a post-mitochondrial supernatant for metabolic activation, although acridine was mutagenic only in the absence of such an activating system. An examination of the effect of the metabolizing system's concentration on mutagenicity showed that quinoline, benzo[f]quinoline, and phenanthridine have different optima. In an attempt to uncover active intermediates in aza-arene metabolism, N-oxides of quinoline and phenanthridine were synthesized and found to be non-mutagenic, and coincubation with the epoxide hydrase inhibitor trichloropropylene oxide did not affect the mutagenic activity of quinoline or phenanthridine.
TL;DR: Results indicate that selenite and mercury mutually antagonize their ability to cause DNA damage leading to the formation of SCEs, and that glutathione in RBCs might play a key role in this antagonism between mercury and selenium.
Abstract: The protective effect of sodium selenite (Na2SeO3) against the cytogenetic toxicity of methyl mercury (CH3HgCl) and mercuric chloride (HgCl2) were investigated on human whole-blood cultures in relation to induction of sister-chromatid exchange (SCE). Both mercurials caused a dose-dependent increase in SCEs, methyl mercury being about 5 times more potent than mercuric chloride. Sodium selenite also induced SCEs. However, the simultaneous addition of selenite (1 x 10(-7) -3 x 10(-5) M) to cell cultures containing either methyl mercury (3 x 10(-6) M) or mercuric chloride (1 x 10(-5) M) prevented the induction of SCEs by the mercurial in a clear dose-related manner. When selenite and mercurial were simultaneously added at a molar ratio of 1:2 Na2SeO3:CH3HgCl, or 1:1 Na2SeO3:HgCl2, cells from treated cultures showed no increase in the SCE frequency. These results indicate that selenite and mercury mutually antagonize their ability to cause DNA damage leading to the formation of SCEs. The formation of bis(methylmercuric)selenide, (CH3Hg)2Se, from Na2SeO3 and CH3HgCl, or a high molecular complex consisting of glutathione-Se-Hg from Na2SeO3 and HgCl2 involving the participation of glutathione in RBCs might play a key role in this antagonism between mercury and selenium.
TL;DR: Both benzoate and sulphite inhibit DNA synthesis in Vicia faba root meristems and complete recovery of mitotic figures and normal chromosome configurations were observed within the first 23-46 h of regrowth.
Abstract: Sodium sulphite and sodium benzoate induce in Vicia faba root meristems: (1) dose-dependent reduction in mitotic figures, (2) intact and severed anaphase bridges, (3) premature chromosome condensation heading to pycnofic nuclei, and (4) chromatin erosion in interphase nuclei. The effects are due to the anions and not due to the sodium ions. Complete recovery of mitotic figures and normal chromosome configurations were observed within the first 23–46 h of regrowth. Recovery was accompanied by severed anaphase bridges and micronuclei of various shapes. Both benzoate and sulphite inhibit DNA synthesis in Vicia faba root meristems. Sulphite was more effective than benzoate.
TL;DR: The enhancing effect of acetonitrile on the mutagenicity of Trp-P-2 was found to be result of enrichment of the active metabolite in the assay system.
Abstract: The effect of adding organic solvents to the pre-incubation mixture in the Salmonella/mammalian microsome assay was examined in tests of the tryptophanpyrolysate mutagens, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Acetonitrile enhanced the mutagenic activity of Trp-P-1 and Trp-P-2 by an order of magnitude under optimal conditions. Strong enhancement of mutagenicity was also observed for the addition of ethanol, methanol, tetrahydrofurfuryl alcohol, tetrahydrofuran, 1,2-dimethoxyethane and N,N-dimethylformamide. The enhancing effect of acetonitrile on the mutagenicity of Trp-P-2 was found to be result of enrichment of the active metabolite in the assay system.
TL;DR: The nitroimidazole derivatives used in human therapy have shown a strong mutagenic activity in bacterial tests using Ames strains of Salmonella typhimurium, but the strong positive response on TA100 was greatly reduced on the nitroreductase-deficient strain TA100 Frl.
Abstract: The nitroimidazole derivatives used in human therapy have shown a strong mutagenic activity in bacterial tests using Ames strains of Salmonella typhimurium. Our study compared the response of 4 products of this family on bacterial target cells as well as on mammalian target cells (Chinese hamster V79 cells).
The strong positive response on TA100 was greatly reduced on the nitroreductase-deficient strain TA100 Fr1. Furthermore, no mutagenic activity was found in V79 mammalian cells that we examined for ouabain and 6-thioguanine resistance.
TL;DR: Several of the compounds examined for their mutagenic activity in S. typhimurium strains TA1535 and TA1537 were highly toxic to the bacteria, and detection of mutagenicity was enhanced by calculating the increase in mutagenIC activity on the basis of the surviving fractions of bacteria.
Abstract: Selected hydrazines and related compounds were examined for their mutagenic activity in S. typhimurium strains TA1535 and TA1537. These in vitro assays were conducted with and without metabolic activation by Aroclor-induced rat-liver enzymes. Relatively high levels of mutagenicity were observed with phenylhydrazine · HCl, methylhydrazine, N′-acetyl-4-(hydroxymethyl)phenylhydrazine, and 4-(hydroxymethyl)benzenediazonium tetrafluoroborate, the stabilized salt of a carcinogenic metabolite of agaritine; only low levels of mutagenicity were observed with other compounds, although most are strong carcinogens. Several of the compounds were highly toxic to the bacteria, and detection of mutagenicity was enhanced by calculating the increase in mutagenic activity on the basis of the surviving fractions of bacteria.
TL;DR: After tetracycline hydrochloride (TC) treatment for 48 h, 8-azaguanine-resistant mutants were obtained in a population of cultured Chinese hamster cells and mutation frequency remained constant thereafter.
Abstract: After tetracycline hydrochloride (TC) treatment for 48 h, we obtained 8-azaguanine-resistant mutants in a population of cultured Chinese hamster cells. Optimal expression of mutation was reached after about 5 days, and mutation frequency remained constant thereafter. There was a gradual increase in the yield of mutants with increasing doses of TC, and measurable yield was observed at a dose as low as 10 μ g of TC per ml. When the cells, before or after the TC treatment, were grown in presence of l -ascorbic acid (10 or 20 μg/ml) for 48 h, there was significant decrease in the frequency of mutation induced by TC. If lk -ascorbic acid were present at the same concentration during the treatment with TC, no significant influence on the induction of mutants by TC was detected.
TL;DR: 1,2,3-Tribromopropane induced dominant lethal mutation especially in the early spermatid stage of SD male rats with 5 halogenated 3-carbon compounds that are structurally similar to a known mutagen 1,2-dibromo-3-chloroproane (DBCP).
Abstract: Dominant lethal studies were conducted in SD male rats with 5 halogenated 3-carbon compounds that are structurally similar to a known mutagen 1,2-dibromo-3-chloropropane (DBCP). 1,2,3,-Tribromopropane induced dominant lethal mutation especially in the early spermatid stage. This finding was almost the same as that obtained after DBCP treatment. The estimated dominant lethal mutation index of a group treated with 1,2-dibromopropane was marginal at week 1 of testing. On the other hand, 1-bromopropane, 1,2,3-trichloropropane and 1-chloropropane produced negative responses for induction of dominant lethals.
TL;DR: A series of aliphatic epoxides were tested for their ability to induce forward mutations in the yeast Schizosaccharomyces pombe, and for all the compounds under study, a linear dose-response relationship was found.
Abstract: A series of aliphatic epoxides were tested for their ability to induce forward mutations in the yeast Schizosaccharomyces pombe . For all the compounds under study, a linear dose-response relationship was found, and the ranking of the relative specific activity was: epichlorohydrin > ethylene oxide > glycidol > 1,2-epoxybutane > 1,1,1-trichloropropylene oxide > propylene oxide > 2,3-epoxybutane. The influence of the metabolic conversion of the epoxides by the mouse-liver S9 fraction was also investigated. In such conditions, except for the 2,3-epoxybutane, the genetic activity of epoxides seems to be reduced.
TL;DR: The background incidence did vary from a uniform distribution across the karyotype with increasing incidences in chromosomes 1 and 2 and those of the B group, and decreasedincidences in the E, F, and G groups.
Abstract: Nickel is a recognized carcinogen to which the general population is being increasingly exposed. A nickel-induced alteration in the incidence of sister-chromatid exchanges in cultured lymphocytes has been investigated. Human lymphocytes from a single donor were cultured in media containing various concentrations of nickelous chloride from 10 −6 to 10 −3 M and a control culture containing no added nickel. A significantly increased incidence of exchanges over background was induced at 1.19 × 10 −4 M as indicated by a Student's t -test. A concentration/response curve was generated up to 5 × 10 −4 M where the nickel concentration was lethal to the cells. The nickel response was analyzed by a chi-square test for any variation in location of activity across the karyotype and no differences were detected. The background incidence did vary from a uniform distribution across the karyotype with increased incidences in chromosomes 1 and 2 and those of the B group, and decreased incidences in the E, F, and G groups.
TL;DR: When compared to known mutagens like ultraviolet light, X-rays and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), ozone appeared to be a weak mutagen.
Abstract: The mutagenicity and recombinogenicity of the atmospheric pollutant, ozone, were investigated in several strains of Saccharomyces cerevisiae. It was observed that ozone induced a variety of genetic events, such as forward and reverse mutations as well as gene conversion and mitotic crossing-over. However, when compared to known mutagens like ultraviolet light, X-rays and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), ozone appeared to be a weak mutagen.
TL;DR: The influence of dietary selenium on the mutagenic activation of 7,12-dimethylbenz[ a ]anthracene (DMBA) by rat liver S9 was studied using the Ames test as mentioned in this paper.
Abstract: The influence of dietary selenium on the mutagenic activation of 7,12-dimethylbenz[ a ]anthracene (DMBA) by rat liver S9 was studied using the Ames test. Rats received supplemental selenium, as sodium selenite, in the drinking water or in the diet. All rats additionally received 0, 20, 50, 100, or 500 mg Aroclor 1254 per kg body weight. Revertant counts decreased 72 and 31% at the 20- and 100-mg/kg induction levels, respectively, with S9 preparations from rats given selenium supplementation, compared to controls. No significant effect of selenium on S9 preparations was observed in rats treated with 500 mg/kg Aroclor. Preparations of S9 from rats receiving 2.5 ppm Se in their diet produced 46, 84 and 70% less revertants than controls at the 20-, 50- and 100-mg/kg induction levels. Increasing the selenium concentration in the diet to 5 ppm reduced the revertant counts by 71, 68 and 65%, at the 20-, 50- and 100-mg/kg induction level of Aroclor, respectively. Dietary selenium supplementation was shown to decrease the mutagenic activation of DMBA by liver microsomes. These studies indicate that in vivo selenium supplementation may reduce susceptibility to the action of various carcinogens.
TL;DR: A lymphocyte culture system was used to study cytogenetic effects in rats after they had been exposed to genotoxic agents in vivo, and the sensitivity of the test system was demonstrated by using cyclophosphamide.
Abstract: A lymphocyte culture system was used to study cytogenetic effects in rats after they had been exposed to genotoxic agents in vivo. The sensitivity of the test system was demonstrated by using cyclophosphamide. The SCE frequencies in lymphocytes of cyclophosphamide-treated rats (13.3 mg/kg; i.p.) was increased about 4-fold compared with those in lymphocytes from untreated rats. Female rats of the strain Wistar II were exposed to cigarette smoke from 30 cigarettes per day in an inhalation chamber. Lymphocyte cultures were performed after an acute exposure and after treatment for 4 weeks. After both treatments, the investigations of chromosomes with regard to SCEs did not reveal any effect.
TL;DR: 6 alpha-chloroepoxides are considered likely to be the active intermediates of the carcinogenic parent halo-olefins and mutagenicity studies are considered relevant in assessing the carcinogenicity of the parent hydrocarbons.
Abstract: 6 α-chloroepoxides have been tested for in vitro activity in a variety of systems. The epoxides were cis- and trans-1-chloropropene oxide, cis- and trans-1,3-dichloropropene oxide, trichloroethylene oxide and tetrachloroethylene oxide. The epoxides were assayed for mutagenicity in the absence of metabolic activation in S. typhimurium TA1535 and E. coli WP2 uvrA and for preferential inhibition of growth of DNA-repair-deficient E. coli. All 6 epoxides possessed DNA-modifying activity as evidenced by their ability to preferentially inhibit DNA polymerase-deficient E. coli. All of the test chemicals except trichloroethylene oxide were mutagenic for S. typhimurium and all except trichloroethylene oxide and tetrachloroethylene oxide were mutagenic for E. coli WP2 uvrA. Cis- and trans-1,3-dichloropropene oxide were the most potent mutagens and DNA modifiers. For all cases, the cis isomers were more active than the corresponding trans isomers. α-Chloroepoxides are considered likely to be the active intermediates of the carcinogenic parent halo-olefins. These mutagenicity studies are considered relevant in assessing the carcinogenicity of the parent hydrocarbons.