Mutagenic action of a series of epoxides

The mutagenicity of a series of 13 epoxide compounds was studied using a bacterial plate assay system. The histidine-dependent tester strains TA98 (for frameshift mutagens) and TA100 (for base-pair substitution mutagens) of Salmonella typhimurium were used. Mutagenicity was evaluated both with and without the addition of rat liver microsomal extract. Dieldrin, diglycidyl ether of bis phenol A and 3 of its homologues were not mutagenic. Allyl glycidyl ether, n-butyl glycidyl ether, vinyl cyclohexene diepoxide, glycidol, glycidaldehyde, diglycidyl ether, diepoxybutane and diglycidyl ether of substituted glycerine were mutagenic in the TA100 strain, causing reversion of the bacteria to histidine independence. Dose—response curves of the mutagenicity of the latter 4 compounds were obtained. On a molar basis, glycidaldehyde was about 20–50 times more potent in producing mutation that were the other 3 epoxides in the dose—response test. In general, the mutagenicity of the epoxides was not enhanced or diminished by the addition of microsomal extract.     

Mutagenic action of methyl 2-cyanoacrylate vapor

Alkyl 2-cyanoacrylate adhesives were tested for mutagenicity in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1538. Both a normal spot test and a spot test specially designed to test volatile compounds were used. The adhesives were also tested in the plate incorporation assay. These investigations showed that methyl 2-cyanoacrylate adhesives are mutagenic in strain TA100. The spot test for volatile compounds showed that it is the vapors from the methyl 2-cyanoacrylate monomer that are responsible for the mutagenic effect. One can conclude that working with methyl 2-cyanoacrylate adhesives entails exposure to vapors with a mutagenic effect and may therefore pose a carcinogenic hazard. Because the adhesives are used in industry, their mutagenic effect has a special importance in work environment.     

Mutagenic action of O-methlhydroxylamide on transforming DNA

The mutagenic effect of O-methylhydroxylamine (OMHA) on transforming DNA of Bacillus subtilis was studied. In accordance with the earlier reported chemical and functional data, the mutagenic effect was observed at 4.5 and 6.0 pH. An increase in pH caused a decrease in the rate of mutagenesis, though the maximal level of mutagenesis was equal at both values of pH. The results obtained with recipients defective in the system of UV-repair revealed that both products of reaction of OMHA with the cytosine-base of DNA, N4-metoxycytidine and N4-metoxy-6-metoxyamino-5,6-dihydrocytidine, are effectively eliminated through the system of UV repair.     

Mutagenic action of cadmium chloride in mammals

The mutagenic effect of cadmium chloride on somatic cells of F1 hybrid mice CBA X C57B1/6J in vivo and on an established line of CHO-ATZ-2 Chinese hamster cells in vitro has been studied. The induction of micronuclei has been demonstrated in mouse marrow cells as well as induction of point mutations at loci controlling the synthesis of hypoxanthine-phosphoribosyltransferase, thymidine kinase, adenine phosphoribosyltransferase and the resistance of Na+/K+ ATPase to ouabain in the cell line CHO-AT-2. A peak of mutagenic activity under the action of subtoxic doses of cadmium chloride has been revealed.     

Mutagenic action of a series of epoxides.

The mutagenicity of a series of 13 epoxide compounds was studied using a bacterial plate assay system. The histidine-dependent tester strains TA98 (for frameshift mutagens) and TA100 (for base-pair substitution mutagens) of Salmonella typhimurium were used. Mutagenicity was evaluated both with and without the additon of rat liver microsomal extract. Dieldrin, diglycidyl ether of bis phenol A and 3 of its homologues were not mutagenic. Allyl glycidyl ether, n-butyl glycidyl ether, vinly cyclohexene diepoxide, glycidol, glycidal-dehyde, diglycidyl ether, diepoxybutane and diglycidyl ether of substituted glycerine were mutagenic in the TA100 strain, causing reversion of the bacteria to histidine independence. Dose-reponse curves of the mutagenicity of the latter 4 compounds were obtained. On a molar basis, glycidaldehyde was about 20-50 times more potent in producing mutation that were the other 3 epoxides in the dose-response test. In general, the mutagenicity of the epoxides was not enhanced or diminished by the addition of microsomal extract.     

Mutagenic action of different alcohols in an experiment

Ethanol, ethylene glycol and glycerine induce chromosomal aberrations in cells of the rat bone marrow and disturb a genetic apparatus of male sex cells at the stage of late spermatids. The cytogenetic activity of ethylene glycol depends on its dose. Phenobarbital stimulates the cytogenetic activity of ethanol and ethylene glycol.     

Mutagenic action of hydroxylamine and methoxyamine on yeast

Summary Hydroxylamine (HA) in 0.1-2M concentration induces in yeast mutation and recombination. Cell survival, and reversion induction show a striking variation from one experiment to another (Figs. 1, 3). There is no clear-cut dose-dependence (Fig. 2). HA inhibits respiration, alcohol dehydrogenase and catalase activities (Tables 1, 2, 4). However, these effects are at least partly reversed when the HA-treated cells are incubated for 1 h in phosphate buffer (Fig. 4, Tables 3 and 6). Catalase inhibition by 10-²M HA does not induce recombination (Table 5). Acetoxime, pyruvoxime and glucosoxime do not seem to be mutagenic (Table 7).The level of free HA in a homogenate of cells treated for 3 h with 1 M HA, without postincubation in buffer is ca. 10-²M.It is suggested that within the yeast cells HA undergoes decomposition into free radicals and peroxide, which directly or through chain reactions induce DNA damages. The direct reaction of HA with cytosine, if it occurs at all, does not seem to play an important role in HA mutagenesis in yeast.     

Mutagenic action of alkylating agents on prophage lambda

The lethal and mutagenic effects of 7 alkylating agents: N-nitroso-N-methylurea (NMU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), nitrogen mustard (HN2), mitomycin C (MC), bifunctional acridine mustard (AM)--and of cyanate (KNCO) on heat inducible lambda cI857 prophage were studied. After treatment of lysogenic cells with mutagens, prophage was heat-induced either immediately or after 90 min incubation in nutrient broth and c mutants forming clear plaques at 32 degrees C were scored. NMU (0.02 M) when immediately induced with heat, induces c mutants very efficiently (maximal yield 10%) not only in the wild-type cells but also in repair-deficient mutants recA13, lexA102, uvrA6 umuC36, recF143, xthA9, polA1, uvrD3 and uvrD502. These data show that NMU-induced mutations are fixed as replication errors due to mispairing modified bases. After delayed heat induction, the prophage survival enhances and the frequency of c mutations declines considerably in host cells of all repair genotypes tested. Carbamoylation is not involved in the mutagenic action of NMU, because KNCO (0.02 M) has a very slight lethal effect and does not induce mutations. MNNG (100 micrograms/ml) and EMS (0.1 M) also induce mutations by replicative mechanism, because maximal yield of c mutations does not depend on RecA+ and is about 15 and 2%, respectively. MMS is a mutagen of the repair type, since its mutagenic action is suppressed by recA mutation of the host. NH2 only inactivates prophage, but does not induce mutations. MC (50 micrograms/ml) and AM (150 micrograms/ml) induce mutations rather inefficiently (the maximal yield 0.1 and 0.3%, respectively) both in recA+ and recA- hosts. The mutagenic action of these agents is probably due to intercalation.     

Mutagenic and carcinogenic action of antimicrobial surface-active substances

The study on the mutagenic activity of commercial synthetic cationic, anionic, amphoteric and nonionogenic surface active substances with antimicrobial properties demonstrated that they had no mutagenic effect on the microbial test systems, i.e. the histidine-deficient strains of Salmonella typhimurium on direct contact and under conditions of metabolic activation in vitro and in vivo. The cationoactive preparation B Kh-14 with the benzyl radical adjoining the nitrogen atom and linear hydrophobic C13H27 with the amide group having a pronounced antimicrobial effect on gram-positive and gram-negative bacteria and fungi showed no carcinogenic activity in the experiments with its long-term action on the urinary bladder mucosa and skin of rats, guinea-pigs and dogs.     

Mutagenic action of nitrous acid on prophage lambda

The lethal and mutagenic effects of nitrous acid (0,1 M NaNO2 in 0,1 M acetate buffer, pH 4.6) on prophage lambda cI857 ind- were studied in the wild-type cells of Escherichia coli and in 9 repair-deficient mutants: uvrA6, uvrA6 umuC36, uvrD3, uvrE502, polA1, recA13, lexA102, recF143 and xthA9. After treatment with HNO2, the prophage was heat-induced either immediately or after 90 min incubation in broth at 32 degrees C. The prophage survival after delayed induction was considerably higher than after immediate induction. The lethal action of HNO2 was highly expressed in uvrA- and uvrE- lysogens after delayed induction. The frequency of temperature-independent c mutants forming clear plaques at 32 degrees C reached 4% in the wild-type host after immediate induction, this value being 10-15% in uvrA, uvrA umuC, uvrD, uvrE, polA and xthA mutants, 0,8% in recF- lysogen and only 0,2-0,3% in recA and lexA mutants. Under these conditions, about 90% of c mutants are generated by recA+, lexA+-dependent repair mechanism (most probably, due to W-mutagenesis). After delayed induction, mutation frequency in the wild-type host declines considerably (down to 0,1%). Analogous phenomenon of mutation frequency decline was registered in uvrA, xthA, recF, polA, uvrE and uvrD lysogens. Under conditions of delayed induction, the frequency of HNO2-induced c mutations only slightly depends on the recA+ and lexA+ gene products and mutations are, apparently, fixed by replication.     

Mutagenic action of heavy ions on Escherichia coli cells

Induction of direct mutations in the lactose operon of E. coli cells by gamma-radiation and accelerated heavy ions with different LET was studied. The experiments were performed with the wild-type PolA and LexA strains. A quadratic dependence of the mutation rate on the dose of different radiations for the wild-type strain and the PolA mutant was observed. However, different types of radiation showed different relative genetic effectivenesses (RGE). The dependence of RGE on LET for the wild-type and PolA strain has a maximum. A LexA strain showed much reduced mutation rates and a linear dose response. The RGE decreased with increasing LET of ionizing radiation.     

Mutagenic and recombinogenic action of pesticides in Aspergillus nidulans

Thirteen pesticides, aminotriazole, benomyl, captafol, captan, dalapon-Na, dichlorvos, dinobuton, dodine, ioxynil, mecoprop, neburon, picloram and tordon were tested for ability to induce (1) point mutations to 8-azaguanine resistance, (2) mitotic crossing-over, and (3) mitotic non-disjunction and haploidization in Aspergillus nidulans. Tests were performed at three different pHs, i.e. 4.5, 7, 8.2. Three of the pesticides, captan, captafol and dichlorvos induced point mutations; dichlorvos also induced a high frequency of mitotic crossing-over and non-disjunction; benomyl induced a very high frequency of non-disjunction whereas aminotriazole induced weakly both types of somatic segregation.     

Mutagenic and recombinogenic action of pesticides in Aspergillus nidulans.

Thirteen pesticides, aminotriazole, benomyl, captafol, captan, dalapon-Na, dichlorvos, dinobuton, dodine, ioxynil, mecoprop, neburon, picloram and tordon were tested for ability to induce (1) point mutations to 8-azaguanine resistance, (2) mitotic crossing-over, and (3) mitotic non-disjunction and haploidization in Aspergillus nidulans. Tests were performed at three different pHs, i.e. 4.5, 7, 8.2. Three of the pesticides, captan , captafol and dichlorvos induced point mutations; dichlorvos also induced a high frequency of mitotic crossing-over and non-disjunction; benomyl induced a very high frequency of non-disjunction whereas aminotriazole induced weakly both types of somatic segregation.     

Mutagenic action of nitroso compounds on Escherichia coli cells]

An attempt to induce some forward and back mutations in two Escherichia coli strains (his- and HfrH requiring thiamine) under the action of the carcinogenic nitrosamines--dimethylnitrosamine (DMN) and diethylnitrosamine (DEN)--is described. For this purpose the cells of E. coli were treated with 5% DMN or 1% DEN for 1 hour at 37 degrees C in 0.14 M NaCl. It was shown that the sensitivity of both strains to both nitrose compounds was not the same. DEN was 5-fold as toxic as DMN for the E. coli cells. DMN and DEN induced neither mutations of resistance to 10(-3) M valine, nor reversions in histidine-dependent strain. These mutations were obtained after the cells were treated with 0.1 M NaNO2. Lethal effects of DMN increased more than in 5 times and the toxicity of DEN did not change in hydroxylating mixture, in which nitrosamines derived to active compounds. Under these conditions both carcinogenes showed a mutagenic activity. DEN proved to be about twice as strong mutagenically as DMN. Thus, in our experiments we could see that DMN and DEN could induce both forward and back mutations in E. coli.     

Mutagenic action of latex polymerization stabilizers in various test systems

The cytogenetic activity of latex polymerization stabilizers (monoethanolamine, triethanolamine and neozon-D) is investigated in three different test systems. It is shown that monoethanolamine and triethanolamine are weak inductors of chromosome breaks in the culture of human lymphocytes and in the Crepis capillaris seeds and induce low levels of gene mutations in the Ames systems. The third stabilizer--neozon-D manifests higher mutagenic activity and definite cytotoxic effect. Monoethanolamine and triethanolamine as to their weak mutagenic effect are recommended as preferable stabilizers to be used in the latex industry.     

Mutagenic action of cadmium on the sex cells of male mice

Possible mutagenic effect of cadmium chloride was studied by determining the frequency of dominant lethal mutations induced in germ cells of male mice. Water solution of CdCl2 was injected intraperitoneally to male mice at doses of 1.0, 2.0 and 4.0 mg/kg. The results obtained did not reveal any mutagenic effect of this compound. The dose of 4.0 mg/kg CdCl2 resulted in the death of spermatocytes and spermatogonia and the sterility of male mice. Cadmium chloride at a dose of 2.0 mg/kg did not affect the frequency of dominant lethal mutation induced by gamma-rays 60Co at a dose of 450 r in germ cells of male mice.