Showing papers on "Ames test published in 1980"
TL;DR: To clarify the mutagenic activity of individual smoke components, 239 compounds, representative of the gaseous and semivolatile phases of tobacco smoke, were assayed for mutagenicity towards 4 histidine-requiring mutants of Salmonella typhimurium.
480 citations
TL;DR: The major stable contributor to this activity has been identified as benzo[a]pyrene-4,5-oxide, a DNA-binding metabolite in biological systems, known to be a strong direct mutagen with Salmonella typhimurium strain TA98.
Abstract: Benzo[a]pyrene deposited on a glass fiber filter reacts rapidly in the dark or light with ambient levels of ozone to yield a mixture of products that display strong direct mutagenicity in the Ames assay. The major stable contributor to this activity has been identified as benzo[a]pyrene-4,5-oxide, a DNA-binding metabolite in biological systems, known to be a strong direct mutagen with Salmonella typhimurium strain TA98.
156 citations
TL;DR: The isolation, identification, and synthesis of one direct-acting mutagen, pyrene-3,4-dicarboxylic acid anhydride, from a sample of diesel exhaust particulates is described, although the compound is only weakly mutagenic in the Ames test.
Abstract: Diesel exhaust particulates contain certain chemicals that are directly mutagenic in the Ames test The isolation, identification, and synthesis of one direct-acting mutagen, pyrene-3,4-dicarboxylic acid anhydride, from a sample of diesel exhaust particulates is described Although the compound is only weakly mutagenic in the Ames test, it is speculated that it is but one of a class of mutagenic dicarboxylic acid anhydrides of various polynuclear aromatic hydrocarbons in diesel exhausts
93 citations
TL;DR: A spontaneous dark variant of the luminous bacterium Photobacterium leiognathi was isolated and the nature of the primary mutation in the dark variant, and the potential use of this luminescence system for detecting different classes of carcinogenic chemical, are discussed.
Abstract: A spontaneous dark variant of the luminous bacterium Photobacterium leiognathi was isolated. The reversion frequency of this variant to genetic-hereditary luminescent cells is greatly increased by nanogram quantities of different base-substitution and frameshift agents. This makes it possible to detect mutagenic compounds at concentrations 100 times lower than that detected by the Ames Test. Curing agents, such as acridine dyes, ethidium bromide and sodium dodecyl sulfate, are also very active in the reversion of this dark variant to the luminous state, but fail to revert it to a genetic-hereditary luminescent type. The nature of the primary mutation in the dark variant, and the potential use of this luminescence system for detecting different classes of carcinogenic chemical, are discussed.
89 citations
TL;DR: M Mammalian cell systems may be not dispensable and are postulated for the primary screening for chemical mutagens and carcinogens in the authors' environment.
Abstract: Chromosome aberration tests (CH-test) in vitro were carried out on more than 400 chemicals from our environment, which included carcinogens and other compounds such as food additives, medical drugs, pesticides and those used in laboratories or industries. All results were compared with those obtained by mutation assays with bacteria (Ames test). Nearly half of these chemicals tested were positive either in the CH-tests or in the Ames tests. Among the chemicals being positive in the CH-tests, however, there were some which were negative in the Ames tests but have been proved to be carcinogenic in animals. Mammalian cell systems, therefore, may be not dispensable and are postulated for the primary screening for chemical mutagens and carcinogens in our environment.
76 citations
TL;DR: The weakest mutagenic activity was shown by 2-chloroethanol and the chloropropanols, while the levels of activity shown by the bromo- and iodoethanols were similar to those of the epoxides.
72 citations
Journal Article•
TL;DR: It is concluded that the contribution of two types of cytochrome P-450, PB-P-450 and MC -P-448, to the metabolic activation is different among various species of chemical carcinogens.
Abstract: Rabbit antisera were prepared against two molecular species of cytochrome P-450, PB-P-450 (major cytochrome P-450 component of the liver microsomes of phenobarbital-treated rats) and MC-P-448 (major cytochrome P-450 component of the liver microsomes of 3-methylcholanthrene-treated rats), purified from the liver microsomes of phenobarbital-treated and 3-methylcholanthrene-treated rats, respectively, and utilized in examining the role of these two molecular species of cytochrome P-450 in the metabolic activation of chemical carcinogens in the Ames test system. The specificity of the antibodies used in this study was examined and confirmed by Ouchterlony double-diffusion tests and by inhibition studies on microsomal benzo( a )pyrene hydroxylase, 7-ethoxycoumarin O -deethylase, and benzphetamine N -demethylase activities.
Studies on the effect of the antibodies on the mutagenicities of benzo( a )pyrene, 7,12-dimethylbenzanthracene, 3-methylcholanthrene, 2-acetylaminofluorene, 2-naphthylamine, o -aminoazotoluene, N -nitrosodimethylamine, and aflatoxin B1 were carried out. The mutagenicities of benzo( a )pyrene and 7,12-dimethylbenzanthracene were inhibited by 82 and 85% by antibody against MC-P-448 (anti-MC-P-448 immunoglobulin), respectively, and were not inhibited by antibody against PB-P-450 (anti-PB-P-450 immunoglobulin) at all. The mutagenicities of 2-naphthylamine, o -aminoazotoluene, and 2-acetylaminofluorene were inhibited by 80, 70, and 60% by anti-MC-P-448 immunoglobulin and also inhibited by 25, 30, and 35% by anti-PB-P-450 immunoglobulin. The two antibodies had identical inhibitory action on the mutagenicities of N -nitrosodimethylamine and 3-methylcholanthrene, which were inhibited by 50 and 60%, respectively. The mutagenicity of aflatoxin B1 was inhibited by 30 and 75% by anti-MC-P-448 immunoglobulin and anti-PB-P-450 immunoglobulin, respectively.
It is concluded that the contribution of two types of cytochrome P-450, PB-P-450 and MC-P-448, to the metabolic activation is different among various species of chemical carcinogens.
65 citations
TL;DR: Two techniques allowing the determination of the mutagenicity of lipophilic compounds such as mineral oils with the Ames test have been developed by using benzo[a]pyrene dissolved in white oil as a synthetic reference oil, with mixed results.
Abstract: Two techniques allowing the determination of the mutagenicity of lipophilic compounds such as mineral oils with the Ames test have been developed by using benzo[a]pyrene (BP) dissolved in white oil as a synthetic reference oil. The first technique involves prior extraction of polynuclear aromatic hydrocarbons (PAH) with dimethyl sulfoxide. In the second method, which proved simpler and of more general use, the compounds to be tested are directly dispersed in aqueous medium with Tween 80. The use of these techniques made possible the study of mutagenicity of various kinds of mineral oil. Mutagenic activity was found in used crankcase oils, and also in petroleum distillates but much less in solvent-refined oils. A good correlation was observed between mutagenic activity and PAH content but not BP content of oils. Because of their peculiar response to the test, petroleum distillates were studied in more detail. When added in low amounts to pure PAH compounds such as BP, they enhanced its mutagenic activity (enhancement). When added in higher amounts, on the contrary, these oils completely inhibited BP mutagenic activity (inhibition effect). Both effects correlated well with the PAH content and the mutagenic activity of the petroleum distillates tested. These results explain the abnormal dose-response curves curves obtained with these petroleum distillates and the negative results regarding their mutagenic activity reported in earlier studies. A likely explanation is discussed for the enhancement and inhibition effects.
61 citations
TL;DR: Participates emitted from diesel engines contain substances which produce mutations in the bacterial assay known as the Ames Salmonella/microsome test, and the limitations and value of the Ames test data are discussed here.
Abstract: Participates emitted from diesel engines contain substances which produce mutations in the bacterial assay known as the Ames Salmonella/microsome test. The limitations and value of the Ames test data are discussed here.
54 citations
TL;DR: The enhancement of mutagenic potency of AFB1 by phenolic antioxidants suggests a specificity with respect to the chemical nature of USAF1, particularly in studies with polycyclic aromatic hydrocarbons.
Abstract: The Ames assay employing Salmonella typhimurium TA100 and TA98 was used to investigate potential interactions between aflatoxin B1 (AFB1) and the phenolic antioxidants butylated hydroxytoluene, butylated hydroxyanisole, and propyl gallate. AFB1 doses were within the linear response range, and the antioxidants were used at levels of 0 to 50 micrograms per plate. All three antioxidants were nonmutagenic in either bacterial tester strain, with or without the hepatic S-9 enzyme preparation; toxic effects were observed at doses higher than 20 micrograms per plate. Butylated hydroxytoluene and butylated hydroxyanisole substantially increased AFB1-induced mutagenesis in the two tester strains with microsomal activation. The addition of 5 to 20 micrograms of butylated hydroxytoluene or hydroxyanisole to 5 to 20 ng of AFB1 per plate caused more than a twofold increase in the number of His+ revertants. Addition of propyl gallate resulted in only a moderate increase in the number of revertants. Whereas several anticarcinogenic and antimutagenic effects by phenolic antioxidants have been reported, particularly in studies with polycyclic aromatic hydrocarbons, the enhancement of mutagenic potency of AFB1 by these compounds suggests a specificity with respect to the chemical nature of AFB1.
54 citations
TL;DR: The results obtained clearly show that all water samples derived from the river Rhine and its branches contain mutagenic activity as discussed by the authors, primarily with strain TA 98 after metabolic activation (rat liver microsomal enzymes).
TL;DR: The mutagenic action of 3 coccidiostatic chinoxaline-N-oxide derivatives, quindoxin, carbadox and olaquindox derivatives, was investigated by Luria and Delbrück's fluctuation test, with Klebsiella pneumoniae and Escherichia coli K12 as test organisms.
Abstract: The mutagenic action of 3 coccidiostatic chinoxaline-di-N-oxide derivatives, quindoxin, carbadox and olaquindox, was investigated by Luria and Delbruck's fluctuation test, with Klebsiella pneumoniae and Escherichia coli K12 as test organisms. These compounds were mutagenic at very low concentrations (2 × 10−5–500 × 10−5 mmole/l). In the Ames test they showed a mutagenic action without metabolic activation with Salmonella typhimurium TA98 and TA100 at concentrations of 0.001–0.1 mmole/l in the top agar. Hence, these compounds cause both base-pair substitutions and frame-shift mutations. When Saccharomyces cerevisiae D4 was cultivated in the presence of the compounds, an increase in the mitotic gene conversions was observed. Certain other N-oxides also showed a mutagenic action in the fluctuation test. With Klebsiella pneumoniae, 4-nitroquinoline 1-oxide was mutagenic at a concentration of 0.005 mmole/l, quinoline 1-oxide at 10 mmole/l and benzofuroxan at 0.01 mmole/l. In this test no mutagenic action was found with 4-nitropyridine 1-oxide, pyridine 1-oxide or 4-picoline 1-oxide. With Salmonella typhimurium TA98 and TA100, 4-nitroquinoline 1-oxide, benzofuroxan and 4-nitropyridine 1-oxide were mutagenic, whereas quinoline 1-oxide, pyridine 1-oxide and 4-picoline 1-oxide were not. In contrast, with the fluctuation test, 4-nitroquinoline 1-oxide appeared to be more mutagenic than quindoxin, carbadox and olaquindox in the plate incorporation test.
TL;DR: The genotoxicity of the antihypertensive agents hydralazine and dihydralazine was tested in mammalian cells and bacteria and support the observation that hydralazines is carcinogenic in mice.
Abstract: The genotoxicity of the antihypertensive agents hydralazine and dihydralazine was tested in mammalian cells and bacteria. Both drugs elicited DNA repair in rat hepatocyte primary cultures. In the Ames test, both with and without an S-9 fraction, hydralazine was mutagenic in strains TA100 and TA1537, whereas dihydralazine was weakly mutagenic in strain TA1537. These findings support the observation that hydralazine is carcinogenic in mice. The carcinogenicity of many chemicals results from interaction with DNA. Since these studies demonstrate that hydralazine and dihydralazine damage DNA in mammalian cells, these drugs should be viewed as potential human carcinogens.
TL;DR: A set of 13 substituted (o-phenylenediamine)platinum dichlorides has been studied in the Ames test using Salmonella typhimurium and shows that the most important determinant of mutagenicity by substituents (X) is electron withdrawal via through resonance.
Abstract: A set of 13 substituted (o-phenylenediamine)platinum dichlorides has been studied in the Ames test using Salmonella typhimurium (TA-92). These cis-platinum compounds are mutagenic without activation by microsomes. The following correlation equation shows that the most important determinant of mutagenicity by substituents (X) is electron withdrawal via through resonance: log 1/C = 2.23 sigma sigma minus + 5.78. C in this expression is the molar concentration of compound producing 30 mutations/10(8) bacteria initially delivered above background mutation, and sigma minus is the Hammett constant obtained from substituted anilines.
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TL;DR: The fluctuation test is an assay for the detection of mutation induction in bacteria by chemicals, carried out in liquid medium, and scored by counting the number out of around 50 tubes or wells that turn yellow.
Abstract: The fluctuation test is an assay for the detection of mutation induction in bacteria by chemicals, carried out in liquid medium, and scored by counting the number out of around 50 tubes or wells that turn yellow. It is suitable for the Ames Salmonella strains or for Escherichia coli WP2 trp and its derivatives. Calcium precipitated microsomes, S9 fraction or freshly prepared hepatocytes can be incorporated for metabolic activation. It is comparable to the Ames test in its ability to detect mutagens and carcinogens and generally shares the limitations of that test as regards extrapolation to animals and man. Its disadvantages are that it is marginally slower and slightly more labour intensive than the Ames protocol. For certain applications, however, these disadvantages may be offset by the advantages of somewhat greater sensitivity, ability to be automated, and facility for using hepatocytes for metabolic activation. The test is particularly suitable for the testing of aqueous samples containing low levels of mutagen.
TL;DR: The compound increased in concentration upon anaerobic incubation of feces at 37 C and this increase was prevented by cold, air, and antimicrobial agents, suggesting that the fecal flora produces the compound.
Journal Article•
TL;DR: The liver cell-mediated assay may be an important adjunct to the battery of short-term tests for carcinogenicity prescreening and correlated better than that in the Ames assay with overall carcinogenic potency in the hamster.
Abstract: The mutagenic activity of N -nitrosobis(2-oxopropyl)amine (BOP), N -nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), N -nitrosobis(2-hydroxypropyl)amine (BHP), N -nitrosomethyl-2-oxopropylamine (MOP), and N -nitrosomethyl-2-hydroxypropylamine (MHP) was examined in the Ames liquid incubation assay, using hamster liver homogenate for metabolic activation, and in the hamster liver cell-mediated V79 cell assay. At similar concentrations, the cell-mediated assay showed a greater mutagenic response over background to these nitrosamines than did the bacterial assay. Also, the relative mutagenic potency in the cell-mediated assay (MOP > MHP > BOP > HPOP > BHP) correlated better than that in the Ames assay (HPOP > MHP ≥ BOP = BHP = MOP) with overall carcinogenic potency in the hamster (MOP > BOP > HPOP > BHP). The liver cell-mediated assay may be an important adjunct to the battery of short-term tests for carcinogenicity prescreening.
TL;DR: It appears that every ellipticine derivative having significant inhibitory effects on hydroxylation of benzo(a)pyrene or mutagenicity of 3-methylcholanthrene also exhibits a very good affinity for microsomal cytochromes P-450.
TL;DR: Rat colon mucosa microsomes contain a competent mixed function oxidase system that hydroxylates the N‐methyl drugs benzphetamine and ethylmorphine, the O‐alkyl drugs p‐nitroanisole and p-nitrophenetole and the polycyclic carcinogen benzo[α]pyrene.
Abstract: Rat colon mucosa microsomes contain a competent mixed function oxidase system that hydroxylates the N-methyl drugs benzphetamine and ethylmorphine, the O-alkyl drugs p-nitroanisole and p-nitrophenetole and the polycyclic carcinogen benzo[alpha]pyrene. The colon system's hydroxylation activities can be selectively induced by pretreatment with phenobarbital or beta-naphthoflavone and can be selectively inhibited by SKF-525A or 7,8-benzoflavone. The colon microsomal system has been solubilized with the non-ionic detergent Renex 690 and resolved by column chromatography into its components cytochrome P-450 and cytochrome P-450 reductase. Colon cytochrome P-450 and cytochrome P-450 reductase can be recombined to reconstitute hydroxylation activity. The colon system is also able to activate carcinogens to mutagenic metabolites as demonstrated in the Ames test system. In addition, the activity of the colon system is markedly increased by pretreatment with gastrointestinal hormones.
TL;DR: Salmonella typhimurium strains which are commonly used in the Ames test for screening potential carcinogens were examined for a number of drug-metabolizing systems, finding that enzymatic and non-enzymatic reaction of immediate carcinogens with thiol groups in s.
TL;DR: The results show no mutagenic effects for the oxidized fractions of deep frying fats nor for the model test substances at higher concentrations, however, limited test reliability resulted from direct toxic effects on bacterial growth.
Abstract: In this study, the Salmonella/microsome mutagenicity test according to Ames et al. (Mutation Res. 31∶347, 1975) was performed in order to detect possible mutagenicity of oxidized deep frying fat fractions. Furthermore, the mono-, di-, tri- and tetrahydroxyoctadecanoic acids and the hydroperoxide of linoleic acid were investigated as model test substances. The Ames assay was carried out with and without metabolic activation including preincubation and liquid culture procedures as described by Mitchell (Mutation Res. 54∶1, 1978). The results show no mutagenic effects for the oxidized fractions of deep frying fats nor for the model test substances. At higher concentrations, however, limited test reliability resulted from direct toxic effects on bacterial growth.
TL;DR: Drosophila oocyte results demonstrate that the extensively used antitumor agent bleomycin has to be considered as mutagenic.
Abstract: Although bleomycin (BLM) induces structural chromosome damage, eg, in human lymphocytes, no, or at best a weak, mutagenicity of this substance has been observed after the application of two well-established mutagenicity screening procedures, the Ames test and the sister-chromatid exchange (SCE) test. After feeding BLM to Drosophila melanogaster males we, too, observed only a weak mutagenicity as measured by the frequency of recessive sex-linked lethal mutations. These results are based on the analysis of postmeiotic germ cell stages (spermatozoa, spermatids). No autosomal translocations were found in the same experiments. BLM was also fed to Drosophila females under conditions similar or identical to those of the experiments with males. We observed a considerable sensitivity of Drosophila oocytes to the induction by BLM of recessive sex-linked lethal mutations and X-chromosomal aneuploidy (nondisjunction and chromosome loss). Our oocyte results demonstrate that the extensively used antitumor agent bleomycin has to be considered as mutagenic.
TL;DR: A highly significant enhancement of mutagenicity occurs with 11 polycyclic aromatic hydrocarbons when 3-methylcholanthrene-induced guinea pig liver S9 is substituted for Aroclor-induced rat Liver S9 in the Ames test.
Abstract: A highly significant enhancement of mutagenicity occurs with 11 polycyclic aromatic hydrocarbons when 3-methylcholanthrene-induced guinea pig liver S9 is substituted for Aroclor-induced rat liver S9 in the Ames test. The use of MC-induced guinea pig liver S9 is particularly valuable for detecting the weak mutagenicity of benz[ c ]acridine, which is barely positive in a standard Ames assay. However, anthracene and phenanthrene, which are generally considered not to be carcinogens, remain non-mutagenic for strain TA100. This enhancement of mutagenicity does not correlate with arylhydrocarbon hydroxylase activities of the various liver preparations and does not apply to certain other non-PAH mutagens, including β-naphthylamine, aflatoxin B 1 and 4-dimethylaminoazobenzene.
TL;DR: Evidence is presented that diffusion of non-mutagenic metabolites of AAF from the Ames test top agar may be responsible for the difference in S9 optima, which is consistent with a model whereby lipophilic non- Mutagenic metabolites accumulate in the microsomes and inhibit further activation.
Abstract: For activation of 2-acetylaminofluorene (AAF) there is an optimal level of rat liver S9 fraction which is considerably lower in the fluctuation test than in the Ames test. The optimal level of S9 is not markedly affected by the dose of AAF used, nor by the ratio of S9 to bacteria, nor by the presence of soft agar. The difference between Ames and fluctuation tests appears to be due to diffusion of some substance or substances from the top agar layer in the Ames test. Diffusion of the co-factors NADP and glucose-6-phosphate is not responsible for the difference in S9 optima, nor is diffusion of soluble S9 constituents although this may considerably affect the performance of the S9 mix. We present evidence that diffusion of non-mutagenic metabolites of AAF from the Ames test top agar may be responsible for the difference in S9 optima. Our results are consistent with a model whereby lipophilic non-mutagenic metabolites accumulate in the microsomes and inhibit further activation. When the metabolites are able to diffuse away, a higher level of S9 will be optimal. The model is consistent with some other phenomena of S9 activation.
TL;DR: A commercial sample of the tuberculostatic drug isoniazid (INH) was found to have a weak mutagenic activity towards Salmonella typhimurium strains TA100 and TA1535, where there was no induction of unscheduled DNA synthesis in human cells by INH except in the presence of manganese.
Abstract: A commercial sample of the tuberculostatic drug isoniazid (INH) was found to have a weak mutagenic activity towards Salmonella typhimurium strains TA100 and TA1535. The addition of a rat or mouse liver homogenate to the test system decreased the mutagenic effect of INH. Hydrazine, an impurity of the INH sample, was also weakly mutagenic in strains TA100 and TA1535, but not to the extent that could account for the mutagenicity of the INH sample. An inhibition of DNA synthesis in human fibroblasts was observed for INH, this effect being potentiated by the addition of manganese to the test system. There was no induction of unscheduled DNA synthesis in human cells by INH except in the presence of manganese. Chemicals/CAS: aroclor 1254, 11097-69-1; hydrazine, 10217-52-4, 13775-80-9, 18500-32-8, 302-01-2, 7803-57-8; isoniazid, 54-85-3, 62229-51-0, 65979-32-0; DNA, 9007-49-2; hydrazine, 302-01-2; Hydrazines; Isoniazid, 54-85-3; Manganese, 7439-96-5; Mutagens
TL;DR: Results indicate that extracts of particulates from Houston air cause a significant number of mutations in bacteria and that the highest frequency of reversions is associated with the smallest particulates.
Abstract: This study was designed to examine suspended air particulates from the Houston atmosphere, Airborne particulates were collected using either a hi-vol sampler (one stage from 0.01 to 25 micrometer) or an Anderson Cascade Impactor, the five stages of which roughly resemble the human respiratory tract. After organic extraction, the Ames assay was used to determine the mutagenic content of extracts, and the ability to induce prophage was assessed. Also DNA-repair-deficient cells were employed to see if the extracts caused DNA damage and what portion of the premutational lesions was repaired in normal cells. Results indicate that extracts of particulates from Houston air cause a significant number of mutations in bacteria and that the highest frequency of reversions is associated with the smallest particulates. An excision repair system is operative in bacteria which is able to assuage damage done to DNA by these extracts. The extracts did not cause prophage induction.
01 Jan 1980
TL;DR: This report is a summary of all findings on nitrotoluene derivatives done in the course of the contract and incorporates portions of Progress Reports Nos. 1, 3, 4, 6 and 7, as well as overall comparisons and conclusions.
Abstract: : This report is a summary of all findings on nitrotoluene derivatives done in the course of the contract. It incorporates portions of Progress Reports Nos. 1, 3, 4, 6 and 7, as well as overall comparisons and conclusions. Acute toxicity data, including rodent LD50s, rabbit irritation tests, guinea pig dermal sensitization test, single-dose metabolism study in rats, and the Ames Salmonella/microsome test were done on 2,4,6-trinitrotoluene, all dinitrotoluene (DNT) isomers (2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-) and (except for the metabolisms study and Ames test) 2-amino-4, 6-dinitrotoluene and 4-amino-2, 6- dinitrotoluene.. Subchronic toxicity tests were done with 2,4-DNT and 2,6-DNT in dogs, rats and mice. Chronic toxicity tests were done with 2,4-DNT in all three species, accompanied by reproductive studies in rats. The metabolism of 2,4-DNT was studied in rats after chronic feeding of 2,4-DNT and in mice, rabbits, dogs, monkeys and in vitro preparations in single-dose studies. (Author)
TL;DR: Salmonella mutants susceptible to base-pair substitution and frame-shift mutagens gave positive results with heat-sterilized milk, particularly after activation by the S-9 fraction of microsomes.