Showing papers on "Ames test published in 1983"
TL;DR: A simple modification of the Salmonella/microsome liquid-incubation procedure improves the sensitivity of the assay for detecting mutagens in human urine and was approximately 14 times more sensitive in detecting the mutagenic activity of benzo[ a ]pyrene.
326 citations
TL;DR: Seventy-six compounds used as artificial flavouring substances in food products were studied for mutagenic properties by the use of the Salmonella/mammalian microsome test (Ames test), Basc test on Drosophila melanogaster and micronucleus test on mouse bone marrow.
194 citations
TL;DR: Seven different test systems were utilized to investigate the genetic activity of chromium compounds and Cr(VI) was active in all the tested systems, except in the induction of DNA damage and DNA repair synthesis in cultured cells.
Abstract: Seven different test systems were utilized to investigate the genetic activity of chromium compounds: infidelity of DNA replication in vitro by DNA polα from calf thymus, damage of DNA detected by alkaline elution in treated mammalian cells or in DNA purified and treated in vitro, DNA repair synthesis in mammalian cells in vitro detected by autoradiography or scintillation counting after labelling with [ 3 H]dThd, gene mutations in the Salmonella typhimurium Ames test, gene mutations (6TG resistance) in cultured hamster cells, sister-chromatid exchanges in different rodent cell cultures, and transformation to anchorage-independent growth of hamster cells in vitro (soft-agar assay). Potassium dichromate and chromium chloride were used as water-soluble Cr(VI) and Cr(III) salts. Several reference mutagens (EMS, MMS, MMC, 4NQO) were included in the single tests as positive controls. Cr(VI) was active in all the tested systems, except in the induction of DNA damage and DNA repair synthesis in cultured cells. Cr(III), on the other hand, was absolutely inactive unless a direct interaction with purified DNA was permitted by the test conditions. The relevance of data from the various tests to the understanding of the mechanisms of the genotoxic activity of chromium is discussed. Effects other than the direct interaction of Cr(III) with DNA are inferred, which can cause infidelity of the DNA polymerase functions.
146 citations
TL;DR: Postmitochondrial supernatant from rat liver and kidney homogenates transformed cysteine into a mutagen that reverted bacteria of the strain Salmonella typhimurium TA100 to histidine independence.
Abstract: Postmitochondrial supernatant from rat liver and kidney homogenates transformed cysteine into a mutagen that reverted bacteria of the strain Salmonella typhimurium TA100 to histidine independence. Glutathione was also activated by kidney postmitochondrial supernatant but not by liver preparations. Hence, important endogenous compounds of mammals are positive in the most commonly used short-term test for carcinogenicity and mutagenicity. Glutathione is positive in the test even at concentrations found in mammalian tissues.
112 citations
TL;DR: The stable isomers of 3- and 4-ring polycyclic aromatic sulfur heterocycles were tested for mutagenicity in the Ames standard plate incorporation test and a liquid pre-incubation modification of the Ames test, finding that Salmonella typhimurium TA100 was the most sensitive strain to mutagenesis by these compounds.
Abstract: The stable isomers of 3- and 4-ring polycyclic aromatic sulfur heterocycles were tested for mutagenicity in the Ames standard plate incorporation test and a liquid pre-incubation modification of the Ames test. Of the 4 three-ring compounds tested, only naphtho[1,2-b]thiophene was mutagenic. Of the four-ring compounds, 7 of 13 were mutagenic in the standard Ames or pre-incubation Ames test. The highest activity for the 4-ring compounds was observed for phenanthrol[3,4-b]thiophene, a compound of approximately the same mutagenic potency in the Ames test as benzo[a]pyrene. The other active 4-ring compounds were of considerable less mutagenic potency than phenanthrol[3,4-b]thiophene. Mutagenicity for two of the 4-ring aromatic thiophenes could only be detected in the liquid pre-incubation Ames test.
Salmonella typhimurium TA100 was the most sensitive strain to mutagenesis by these compounds, followed by TA98. All mutagenesis was indirect, requiring metabolic activation.
81 citations
TL;DR: It is demonstrated that 1,2-dimethylhydrazine is mutagenic in the Ames test when it is incubated together with lithocholic or deoxycholic acid with or without metabolic activation.
Abstract: Even though 1,2-dimethylhydrazine (DMH) is highly carcinogenic in experimental animals, it has not been shown to be clearly mutagenic in any of the short term tests in vitro. The present report demonstrates that DMH is mutagenic in the Ames test when it is incubated together with lithocholic or deoxycholic acid with or without metabolic activation. Such a co-mutagenic effect seems to be restricted to the secondary biliary acids since neither cholic nor chenodeoxycholic acid had the same activity. The secondary biliary acids are present in the colon where they are formed by bacteria. Such a co-mutagenic effect could thus be of importance with regard to the carcinogenic activity of DMH. It could also be relevant to colon carcinogenesis in humans.
72 citations
TL;DR: Results show that natural naphthoquinones are mutagenic when they have only one or two hydroxyl and/or methyl substituents.
Abstract: The mutagenicities of naturally occurring naphthoquinones and benzoquinones were tested by the pre-incubation method with Salmonella typhimurium strains TA98, TA100 and TA2637, which all contain plasmid pKM101. 6 of the 16 naphthoquinones tested, i.e., plumbagin, naphthazarin, 2-hydroxy-naphthoquinone, vitamin K3 (menadione), juglone and 7-methyljuglone, were mutagenic to strain TA2637 with metabolic activation. Except for juglone and 7-methyl-juglone, these compounds also had slight mutagenic effects on strain TA98 with S9 mix. All the mutagenic naphthoquinones contain one or two hydroxyl and/or methyl substituents. The naphthoquinone mompain, which has four hydroxyl groups, was not mutagenic. Unsubstituted beta-naphthoquinone, naphthoquinones with a prenyl side chain and all bi-naphthoquinone derivatives tested were non-mutagenic. None of the 13 benzoquinones examined was mutagenic to any of the strains used with or without metabolic activation. These results show that natural naphthoquinones are mutagenic when they have only one or two hydroxyl and/or methyl substituents.
56 citations
TL;DR: Free histidine as well as histidine in the form of dipeptides present in food samples or biological material interacted with the Ames mutagenicity test, which is indispensable for the avoidance of misinterpretations.
Abstract: Free histidine as well as histidine in the form of dipeptides present in food samples or biological material interacted with the Ames mutagenicity test. This event becomes especially important for test compounds that exert only weak 'mutagenic' effects. Histidine bound to large molecules and methyl derivatives did not affect the Ames test. For the avoidance of misinterpretations, it is therefore indispensable to determine or eliminate the interacting forms of histidine when protein-containing samples are tested in the Ames test. Extraction methods using sorbants and solvents that contain contaminants or can induce chemical reactions with biological test substances should be well controlled or avoided. Solvents such as alcohols, esters and aliphatic hydrocarbons that would minimally react with such test material should therefore be used for extraction.
55 citations
TL;DR: The comutagenic and cocarcinogenic properties of BHT have been demonstrated in tests ranging from the Ames test to cell transformation procedures to in vivo assays, and they are one of the few compounds to have both tumor prophylactic and tumor promoting capacities.
Abstract: Although the average American's daily consumption of BHT can be measured in milligrams, there are numerous reports that BHT causes organ damage in laboratory animals. Only a few genotoxic effects of BHT have been reported, however, including mutagenicity in the abnormal sperm assay and ambiguous results regarding its teratogenicity. More dramatic are the modulatory effects of BHT on the actions of established mutagens and carcinogens. BHT can either enhance or inhibit mutagenic potency, depending on the substance tested. For example, in the Ames test, BHT is antimutagenic towards benzo(a)pyrene, but increases the number of Salmonella revertants induced by aflatoxin B1. BHT is one of the few compounds to have both tumor prophylactic and tumor promoting capacities. It is the temporal sequence in which BHT and carcinogens are administered to test animals which determines how BHT affects the response to these carcinogens. In common with other antioxidants, BHT inhibits the ability of carcinogens to induce tumors in various rodent organs when the animal is given BHT prior to carcinogen treatment. Unlike other antioxidants, however, the number of tumors increase when BHT is administered after carcinogen exposure. The comutagenic and cocarcinogenic properties of BHT have been demonstrated in tests ranging from the Ames test to cell transformation procedures to in vivo assays. These effects are probably mediated by metabolites of BHT, rather than by BHT itself.
52 citations
TL;DR: The Ames test was used to detect the presence of mutagenic/carcinogenic byproducts in ferrate treated water samples that had been spiked with selected priority pollutants as discussed by the authors.
Abstract: The Ames test is used to detect the presence of mutagenic/carcinogenic by‐products in ferrate treated water samples that had been spiked with selected priority pollutants. The gas chromatograph analysis is used to measure the efficiency of removing the substance to be removed but could not be used to detect the production of such by‐products. Negative Ames test results suggested the ferrate treatment was not only effective in removing the substance but also did not produce any remaining mutagenic by‐products during the treatment process. Increasing concern about the chemical pollution of drinking water sources and the possible generation of mutagenic/carcinogenic substances by water and wastewater treatment processes suggests the Ames test could become an index of treatment performance.
48 citations
TL;DR: The sediments of Nagara river and its bystreams were extracted with ether and several kinds of polycyclic aromatic hydrocarbons (PAH) were found, and several peaks were unidentified, but these PAH may contribute substantially to the mutagenicity of this fraction.
Abstract: The sediments of Nagara river and its bystreams were extracted with ether. The mutagenicities of the extracts were determined by the Ames test with Salmonella typhimurium TA100 with S9 mix. The extracts were fractionated on an activated silica-gel column with four kinds of organic solvent, namely iso-octane, iso-octane:benzene (1:1), benzene:ethyl acetate (1:1) and benzene:methanol (1:1). The highest mutagenicity was observed in the iso-octane-benzene fraction of Arata river by using TA100 with S9 mix. Chemical substances in this fraction were identified by GC-MS and GC, and several kinds of polycyclic aromatic hydrocarbons (PAH) were found. Several peaks were unidentified, but these PAH, especially benzo [b] fluoranthene and benzo [a] pyrene, may contribute substantially to the mutagenicity of this fraction.
TL;DR: It has been confirmed that free radicals derived from autoxidation of these substances are responsible for their mutagenicity.
Abstract: Dihydroxyacetone, glyceraldehyde, glyoxal, methyl glyoxal, and glyoxylic acid were found to show mutagenicity on Salmonella typhimurium TA 100. The mutagenicities of these substances were inhibited by the addition of S-9 or some free radical scavengers. The alkaline buffered solutions of these mutagenic substances were found to reduce Nitro Blue tetrazolium chloride. DNA was degraded by the addition of these mutagenic substances. It has also been confirmed that free radicals derived from autoxidation of these substances are responsible for their mutagenicity.
TL;DR: Hamster was the only species which readily activated all amines, and exhibited the highest ethoxyresorufin O-deethylase and dimethylaniline N-oxidase activities.
Abstract: 2-Acetylaminofluorene, 2-aminofluorene, 4-aminobiphenyl, 2-naphthylamine, 2-aminoanthracene and benzidine were assayed for mutagenicity in the Ames test in the presence of hepatic microsomal preparations derived from mouse, hamster, rat, pig and man. Prior to each mutagenicity assay all activation systems were fully characterized with respect to mono-oxygenase and mixed-function amine oxidase activities. All compounds were metabolically activated to mutagens by all activation systems, but with markedly different efficiencies, hamster being the only species which readily activated all amines. The hamster also exhibited the highest ethoxyresorufin O-deethylase and dimethylaniline N-oxidase activities.
TL;DR: In this paper, a series method of Soxhlet extraction, liquid-liquid partition, thin-layer chromatography, and spectrofluorometry was used to quantify carcinogenic and mutagenic compounds extracted from the particulates that adhered to inner surfaces of diesel and gasoline engine mufflers.
TL;DR: Neither DEHP, MEHP, nor EH exhibited any significant mutagenic activity in strains TA-98,TA-100, TA-1535, TA -1537, andTA-1538 in the Ames test or when tested in the L5178Y TK+/- mouse lymphoma cell mutagenicity assay.
Abstract: Di-(2-ethylhexyl)phthalate (DEHP) and its two major metabolites, mono-(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (EH), were tested for genetic activity in both the Salmonella/mammalian microsome mutagenicity (Ames) assay and the L5178Y TK+/— mouse lymphoma cell mutagenicity assay. All chemicals were tested in both the presence and absence of Aroclor-induced liver microsomes prepared from male Sprague-Dawley rats. Dose levels for both assays were selected from preliminary toxicity studies for each chemical. Neither DEHP, MEHP, nor EH exhibited any significant mutagenic activity in strains TA-98, TA-100, TA-1535, TA-1537, and TA-1538 in the Ames test or when tested in the L5178Y TK+/ — mouse lymphoma cell mutagenicity assay.
TL;DR: A statistically significant correlation existed between DNA damage and SCEs and carcinogenic potency and potency in inducing sister-chromatid exchanges (SCEs) in vivo were compared.
Abstract: 16 aromatic amines and azo derivatives were studied. They were: benzidine; 2-acetylaminofluorene; 3'-methyl-p-dimethylaminoazobenzene; o-aminoazotoluene; p-dimethylaminoazobenzene; 2,4-diaminotoluene; 4,4'-oxydianiline; 2,4-diaminoanisole; 4,4'-methylenedianiline; 2-naphthylamine; auramine O; rhodamine B; ponceau MX; 1-naphthylamine; p-aminoazobenzene and aniline. Carcinogenic potency and potency in inducing sister-chromatid exchanges (SCEs) in vivo were compared. SCEs were absolutely not correlated with carcinogenic potency. A lack of correlation was also found with mutagenicity in the Ames test. On the contrary, a statistically significant correlation existed between DNA damage and SCEs.
TL;DR: There are only limited data available concerning its mutagenicity in microbial systems, especially Salmonella typhimurium, and formaldehyde is usually considered a weak mutagen in most microbial Mutagenicity assays.
TL;DR: It is confirmed that the mutagenicity of the nitroheterocyclic compounds is not separated from other biological activities, such as antimicrobial activity.
Abstract: Twenty-five 5-nitroimidazole and two 5-nitrothiazole derivatives were tested for mutagenicity as well as for antibacterial activity in Salmonella typhimurium TA-100 strain. Many of these compounds such as metronidazole, azanidazole, nimorazole, carnidazole, ornidazole, tinidazole, etc are extensively used in human chemotherapy, and some of them were recently synthetized for possible clinical trials as hypoxic cell specific radiosensitizers. Both mutagenic and antibacterial activity were shown for 22 of the test compounds. The high correlation between mutagenic and antibacterial activity supports the hypothesis of a same mechanism for both activities. The present results confirm that the mutagenicity of the nitroheterocyclic compounds is not separated from other biological activities, such as antimicrobial activity.
TL;DR: Findings indicate that arylamine N-hydroxylase is a cy tochrome P-450 dependent enzyme, and the nature of the isozyme of the cytochrome is an important determinant of its mutagenicity.
Abstract: The role of cytochromes P-450 and P-447 in the activation of 4-aminobiphenyl to mutagens in the Ames test was studied using S9 preparations and highly purified isozymes. S9 preparations from beta-naphthoflavone-pretreated rats were more efficient in converting 4-aminobiphenyl to mutagens than the corresponding preparations from phenobarbitone-pretreated animals. Similarly, reconstituted systems comprising purified cytochrome P-447 were twice as efficient as cytochrome P-450 in activating the carcinogen. Of all the known Phase I metabolites of 4-aminobiphenyl, only the N-hydroxy-derivative was mutagenic in the Ames test. These findings indicate that arylamine N-hydroxylase is a cytochrome P-450 dependent enzyme, and the nature of the isozyme of the cytochrome is an important determinant of its mutagenicity.
TL;DR: The utility of the Ames test in screening for potential mutagens may be expanded by a reductive pretreatment utilizing cecal bacteria.
Abstract: Congo red, an azo dye derived from benzidine, and 2-azoxyfluorene, a derivative of 2-aminofluorene, were reduced during overnight incubation with a suspension of rat intestinal bacteria. High performance liquid chromatography and ultraviolet spectral analysis verified the presence of benzidine in extracts of the Congo red incubations and 2-aminofluorene in extracts of the 2-azoxyfluorene incubations. Extracts of the Congo red incubations were mutagenic toward Salmonella typhimurium TA1538 in the presence of a post-mitochondrial activating system, but Congo red was not mutagenic without this reductive pretreatment. Thus, the utility of the Ames test in screening for potential mutagens may be expanded by a reductive pretreatment utilizing cecal bacteria.
TL;DR: Effectiveness of the rec assay was related to the DNA repair-defective nature of the uvrA- recA- genotype of strain WP100, and was more effective than pol tests with E. coli strains W3110/p3478 and strains WP2/WP67.
Abstract: 46 chemicals of various classes and structures, including 30 known animal carcinogens, were evaluated for genotoxic effects using the Escherichia coli rec assay with strains WP2 (wild-type) and WP100 ( uvrA −1 recA − ) in qualitative and quantitative spot tests and in quantitative suspension tests. The rec assay detected 17 of 30 known carcinogens as genotoxic agents, including mitomycin C and diethylnitrosamine, both negative in the Salmonella/Ames test as utilized in these studies. The rec assay in conjunction with the Salmonella/Ames test 30 known carcinogens as genotoxic agents. Azo/aminoazo carcinogens showed little genotoxicity, and the aromatic amine 2-acetylaminofluorene was non-genotoxic in the rec assay. The rec assay was more effective than pol tests with E. coli strains W3110/p3478 and strains WP2/WP67. Effectiveness of the rec assay was related to the DNA repair-defective nature of the uvrA − recA − genotype of strain WP100.
TL;DR: The mutagenicity of coal dust solvent extracts with and without nitrosation was studied using the Salmonella/microsome assay system and mutagenic activity appeared to be independent of metabolic activation.
Journal Article•
TL;DR: There is a good correlation between the increase of mutagenic activity and the contents of the two cytochrome P-450 species in microsomes by administration of various carcinogens to rats.
Abstract: Using the liver 9000 × g supernatant fraction of uninduced rats and monospecific antibodies against microsomal reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase and two inducible forms 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), in the Ames test system, the contributions of these 2 forms of cytochrome P-450 to the mutagenicities of 3-amino-1-methyl-5 H -pyrido[4,3- b ]indole, 2-acetylaminofluorene, and aflatoxin B1 were studied. The mutagenicities of these three carcinogens were completely inhibited by antibody to reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase. The mutagenicities of 3-amino-1-methyl-5 H -pyrido[4,3- b ]indole, 2-acetylaminofluorene, and aflatoxin B1 were inhibited 85, 85, and 40%, respectively, by antibody to MC-P-448 (anti-MC-P-448 immunoglobulin) and also inhibited 5, 30, and 60%, respectively, by antibody to PB-P-450 (anti-PB-P-450 immunoglobulin). These results indicate the importance of these two forms of cytochrome P-450 in the activation of the carcinogens by the liver 9000 × g supernatant fraction of uninduced rats.
We also examined the correlation between the induction of the two forms of cytochrome P-450 and the change of mutagenic activities at various time points after a single dose of various carcinogens to rats. Benzo( a )pyrene and 3-methylcholanthrene induced only MC-P-448 about 15 and 20 times, respectively, as much as that in untreated rats at the maximal levels of induction. The 9000 × g supernatant-mediated mutagenicities of benzo( a )pyrene and 3-methylcholanthrene varied in parallel with the content of MC-P-448 in microsomes, and the induced mutagenicity of benzo( a )pyrene was completely inhibited by anti-MC-P-448 immunoglobulin. o -Aminoazotoluene induced both MC-P-448 and PB-P-450 about 10 and 5 times as much, respectively, while the induced mutagenicity of o -aminoazotoluene was inhibited 90 and 10% by the antibodies to MC-P-448 and PB-P-450, respectively. Both MC-P-448 and mutagenic activity of 2-acetylaminofluorene were induced about three times by a single dose of 2-acetylaminofluorene to rats. Administration of aflatoxin B1 showed neither induction of cytochrome P-450 nor an increase of mutagenic activity of aflatoxin B1. It is concluded that there is a good correlation between the increase of mutagenic activity and the contents of the two cytochrome P-450 species in microsomes by administration of various carcinogens to rats.
TL;DR: In this paper, the performance of a full-scale granular activated carbon (GAC) treatment system in removing mutagens from drinking water obtained from the Ohio River has been evaluated using two bacterial mutagenicity tests.
Journal Article•
TL;DR: The results show that, although Adriamycin and menogarol differ significantly in their bacterial mutagenicity (Ames assay), they have similar genotoxic activity in several mammalian systems.
Abstract: Adriamycin and menogarol are anthracyclines which cause more than 100% increase in life span of mice bearing P388 leukemia and B16 melanoma. Unlike Adriamycin, menogarol does not bind strongly to DNA, and it minimally inhibits DNA and RNA synthesis at lethal doses. Adriamycin is a clinically active drug, and menogarol is undergoing preclinical toxicology at National Cancer Institute. In view of the reported mutagenicity of Adriamycin, we have compared the genotoxicity of the two drugs. Our results show that, although Adriamycin and menogarol differ significantly in their bacterial mutagenicity (Ames assay), they have similar genotoxic activity in several mammalian systems. Adriamycin is strongly mutagenic in the Ames assay with TA98 and TA100. Menogarol is nonmutagenic to TA98 and TA100. For the mammalian cell culture systems, V79 (Chinese hamster) cells are exposed for 2 hr to drug, following which cell survival, induction of sister chromatid exchanges, chromosome damage, and production of mutants resistant to 6-thioguanine are measured. The percentage of survival obtained with the two drugs ranges between 25 and 50% at 0.15 microgram/ml and 5 to 15% at 0.3 microgram/ml. At 0.15 microgram/ml, Adriamycin and menogarol increase the percentage of cells with chromosome damage from a background level of 8.8 to 30 and 22.5%, respectively. The same drug concentration causes a small but significant increase in sister chromatid exchange rate. Both drugs are equally active (increase mutation frequency about 3- to 6-fold above background) in producing 6-thioguanine-resistant mutants. The induction of micronuclei in polychromatic erythrocytes of rats is the most sensitive assay system. Both drugs cause 10- to 15-fold increase in micronuclei at nontoxic doses.
TL;DR: The studies indicate that vitamin K3 is an inhibitor of aryl hydrocarbon hydroxylase and reduces the carcinogenic and mutagenic metabolites in vitro, and inhibits benzo(a)pyrene tumorigenesis in vivo.
Abstract: Vitamin K3 inhibits the conversion of benzo(a)pyrene to its more polar metabolites in an in vitro rat liver microsomal system. Vitamin K3 also inhibits benzo(a)pyrene metabolism in rat liver fragments and reduces its mutagenicity in the Ames test. Higher concentrations of vitamin K3 are required to comparably reduce benzo(a)pyrene metabolism when the microsomal system has been induced with 3-methylcholanthrene. High pressure liquid chromatography analysis of the products of benzo(a)pyrene metabolism shows a uniform reduction of all the metabolic products. When tumors were induced in ICR/Ha female mice by the intraperitoneal injection of benzo(a)pyrene, those mice given vitamin K3 before or both before and after benzo(a)pyrene had a slower rate of tumor appearance and tumor death rate as compared with those receiving benzo(a)pyrene alone. However, vitamin K1 increased the rate of tumor death while vitamin K deprivation and warfarin decreased the rate of tumor appearance and death in benzo(a)pyrene-injected mice. These studies indicate that vitamin K3 is an inhibitor of aryl hydrocarbon hydroxylase and reduces the carcinogenic and mutagenic metabolites in vitro, and inhibits benzo(a)pyrene tumorigenesis in vivo. That vitamin K1 enhances the benzo(a)pyrene effect while warfarin and vitamin K deficiency inhibit benzo(a)pyrene tumorigenesis indicates that vitamin K1, vitamin K deprivation, or possibly blockade of its metabolic cycle also modulates benzo(a)pyrene metabolism in vivo but by a mechanism or at a site different from the vitamin K3 effect. The vitamin K series should be considered as capable of serving a regulatory function in the metabolism of benzo(a)pyrene and possibly other compounds metabolized through the mixed function oxidase system.
TL;DR: A statistical structure-activity model of the Salmonella typhimurium (Ames) test has been devised based on 472 chemicals for which this endpoint has been measured and can be used as a preliminary screen prior to other testing as well as for setting priorities for more detailed investigations.
Abstract: A statistical structure-activity model of the Salmonella typhimurium (Ames) test has been devised based on 472 chemicals for which this endpoint has been measured. The model uses substructural fragments as the independent parameters to explain the difference in mutagenicity of the different chemicals. The model is able to classify 86% of the chemicals into their correct categories; the false-positive rate is 4.7%, and the false-negative rate 5.3%. Approximately 10% of the chemicals cannot be classified by the existing equation. This structure-activity model can be used as a preliminary screen prior to other testing as well as for setting priorities for more detailed investigations.
TL;DR: Positive qualitative and quantitative correlation between UDS, Ames test and alkylating properties (as measured in the 4-nitrobenzyl-pyridine test, NBP) were found.
TL;DR: The mutagenic activities of 2 hydroxyxanthones, gentisin and isogentisin, obtained from the methanol extract of Gentianae radix (Gentianaceae) were investigated and it was estimated that the combined yield of S1 and S2 was about 76 mg, which accounted for 76% of the content ofmutagenic compounds.
Abstract: The mutagenic activities of 2 hydroxyxanthones, gentisin and isogentisin, obtained from the methanol extract of Gentianae radix (Gentianacea) were investigated. The methanol extract of Gentianae radix, which showed mutagenicity in the Ames test in Salmonella typhimurium strain TA100 with S9 mix, was fractionated by column chromatography on Sephadex LH-20, and the fractions were purified by preparative TLC and column chromatography on polyamide. 2 mutagenic materials thus obtained, S1 and S2, each gave a single band on TLC. Identification of S1 and S2 was accomplished by comparing the analytical (mps, elementary analyses) and spectral (UV, IR, mass, NMR) results for S1 and S2 with literature data for gentisin and isogentisin. At doses below 10 μg, S1 (gentisin) and S2 (isogentisin) had similar specific mutagenic activities. At doses of over 10 to 50 μg, the mutagenic activities of S2 and S1 were 19.1 and 6.94 revertants per μg respectively. This much lower activity of S1 than S2 may be a result of its poor solubility owing to the presence of the OMe group at C-3. The combined yield of S1 and S2 was about 76 mg (40 mg as S1 and 36 mg as S2), which accounted for 76% of the content of mutagenic compounds (100 mg) estimated roughly from the total mutagenic activity in the extract of the starting materials (100 g).
TL;DR: It is concluded that there is no overt mutagenic or carcinogenic potential associated with β-adrenergic blocking drug activity.