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At least 109 records · Page 6Linked to original sources
PubMed1985

Absence of mutagenicity in the urine of autopsy service workers exposed to formaldehyde: factors influencing mutagenicity testing of urine.

Hospital autopsy service workers and a matched control group were studied using a battery of genetic monitoring tests performed on samples of blood, semen and urine. The results of the analysis of urine for mutagens are described in this report. The participants in the study were matched with the controls for sex, age and their use of alcohol, tobacco and marijuana. Information was collected on general health, usage of medications and any exposure which might affect the outcome of the study. Individuals were sampled three times at approximately two month intervals. Time weighed average exposures to formaldehyde in the work areas were estimated at 0.61 to 1.32 ppm. Additionally, studies were carried out which examined various parameters affecting the testing of human urine samples for mutagenicity. No increase in mutagenicity was seen in the autopsy workers as compared to the control group. One individual who was receiving metronidazole and one control who smoked two packs of cigarettes per day had significantly mutagenic urine. A large proportion of the exposed individuals had toxic urine while only two of the control individuals had similar toxic urine. The material responsible for the toxicity has been isolated and purified but does not appear to be related to the formaldehyde exposure. Studies on the parameters affecting mutagenicity testing of urine with Salmonella typhimurium suggest that in the plate incorporation assay, TA100, but not TA98, can be affected by exogenous histidine. Furthermore, with the conditions employed in this study, 3 to 4% of labeled histidine added to urine samples was retained by the XAD-2 and subsequently eluted in the urine concentrate. Urinary histidine levels of unconcentrated samples ranged from 112 to 2614 nmol per ml (mean 994 nmol per ml) and the amount of histidine present correlated with the corresponding increases in histidine revertants with strain TA100.

Adult↗
PubMed1981

Mutagenicities of styrene oxide derivatives on bacterial test systems: relationship between mutagenic potencies and chemical reactivity.

The reaction products of deoxyguanosine with 3,4-dimethyl-, p-methyl-, m-methyl-, m-methoxy-, p-bromo-, m-chloro- and unsubstituted styrene oxide were isolated and characterized. The reaction followed second-order kinetics. The reactive site was the N-7 site of guanine. The normal isomer (attack at CH2 of styrene oxides) and the abnormal isomer (attack at CH) were obtained. The Hammett reaction constant (rho) for the normal reaction was +0.42 and that for the abnormal reaction was -1.1. The difference of acid dissociation constant, rate of imidazole ring opening and rate of glycosidic bond cleavage was not found between the normal adduct and the abnormal adduct. Styrene oxides have been tested for toxicity and mutation in a liquid suspension assay using Escherichia coli WP2 and some of its repair deficient derivatives. Salmonella typhimurium TA100 was also employed. The mutation frequency of 3,4-dimethylstyrene oxide was higher in CM571 than in WP2. The greatest mutability was found with the WP2uvrA strain. 3,4-Dimethylstyrene oxide also acted as an inducer of E. coli K-12 (kappa). The mutagenicity of 3,4-dimethylstyrene oxide may depend on a combination of the recA-dependent and recA-independent action mechanisms. The mutagenicities of these compounds in WP2uvrA and TA100 increased in the order: m-chlorostyrene oxide = p-bromostyrene oxide less than m-methoxystyrene oxide less than styrene oxide less than m-methylstyrene oxide less than p-methylstyrene oxide less than 3,4-dimethylstyrene oxide. There was no correlation between the mutagenicities and the total reaction rates. On the other hand, the reaction rates of these compounds for the abnormal reaction correlated with their mutagenicities. The results indicate that the mutagenic effect of a chemical is not dependent simply on the quantity of the adducts, but may vary with structure of its adducts.

Bacteriophage lambda↗
PubMed1980

Relative mutagenicity of antineoplastic drugs and other alkylating agents in V79 Chinese hamster cells, independence of cytotoxic and mutagenic responses.

The mutagenic and cytotoxic effects of 4 antineoplastic drugs, vinblastine, vincristine, adriamycin and nitrogen mustard and of several monofunctional alkylating agents have been assayed in V79 Chinese hamster cells. Vincristine, vinblastine and nitrogen mustard did not significantly increase the frequency of TGRHGPRT- mutants but were were all highly cytotoxic. Adriamycin and the monofunctional alkylating agents were all significantly mutagenic even at the lowest doses tested (approx. 70% survival level). Induced mutant frequency increased linearly with increasing dose whereas dose-response curves for cytotoxicity for these effective mutagens invariably showed a shoulder followed by an exponential decline. At equitoxic doses the relative mutagenic effectiveness was MNU > ENU > EMS > MNNG > MMS greater than or equal to DMS. MNU was approx. 20 times more effective than MMS and DMS. Measurement of the total amount of alkylation and the relative amounts of reaction with individual DNA bases at approx. equitoxic doses of MNU and DMS indicated a significantly higher O6/N7 ratio after MNU (0.15) than after DMS (0.005). However, approx. equal numbers of mutants/10(5) cells/microM O6-Meguanine were induced by these 2 agents. These results support previous conclusions, that mutagenic and cytotoxic responses are independent in V79 cells.

Alkanesulfonates↗
PubMed1982

The chemical activation of non-mutagenic nitrated polycyclic aromatic hydrocarbons to mutagens.

Nitrated polycyclic aromatic hydrocarbons, including carcinogens, may be non-mutagenic in microorganisms because bacterial nitroreductases are unable to reduce their nitro function to proximate mutagenic hydroxylamines. This reduction of the nitro moiety can be accomplished chemically in situ using zinc dust. The procedure, which is compatible with the Salmonella mutagenicity assay, was used to generate mutagens from chemicals which otherwise are non-mutagenic even in the presence of microsomal preparations.

Carcinogens↗
PubMed1985

A comparison of methods for concentrating mutagens in drinking water--recovery aspects and their implications for the chemical character of major unidentified mutagens.

A comparison of techniques for concentrating mutagenic compounds in drinking water has shown that XAD-2 adsorption and dichloromethane extraction have acceptable and almost identical enrichment properties, while purging at an elevated temperature is inappropriate in this context. Quantitatively, the most important drinking water mutagens could only be adsorbed (extracted) after acidification of the water, and even then recovery was far from complete. Recovery experiments with known mutagens from pulp mill effluents have shown that none of the major chlorination-stage mutagens identified thus far can explain the mutagenic activity of extracts from neutral or acidified chlorinated drinking water.

Adsorption↗
PubMed1991

Assessing the use of known mutagens to calibrate the Salmonella typhimurium mutagenicity assay: II. With exogenous activation.

In order to determine the usefulness of selected chemicals as potential reference materials for calibrating the Salmonella assay, two laboratories tested a series of Salmonella mutagens that require exogenous activation. When the variance for individual substances within a bioassay is sufficiently low and the rankings of those substances are of acceptable consistency, they can later be evaluated for use as standard control compounds, as audit materials, and as standard reference materials for comparative bioassay efforts. The purpose of this project, therefore, was to evaluate the variability in the mutagenic response of potential reference chemicals that require exogenous metabolic activation in the standard plate-incorporation Salmonella mutagenicity assay, and to develop ranking criteria for mutagenic activity based on these data. Ten indirect-acting mutagens were tested in two laboratories using Salmonella typhimurium TA100 and an Aroclor-induced rat liver S9. Each laboratory conducted four definitive testing rounds. A different batch of S9 was utilized for every two rounds. Of the 10 chemicals tested only 2-anthramine had a mean slope value greater than 1000 revertants/micrograms. Three chemicals had slope values between 1000 and 100; and five chemicals had slope values between 100 and 10. The remaining compound, 9,10-dimethyl-1,2-benz[a]anthracene, could not be placed into a single category because it had slope values on either side of 100 revertants per mg. Coefficients of variance were low (i.e., below 25% in most cases). The low variability achieved in this study may be accounted for by two parameters of the study. First, based on Claxton et al. (1991a) and the S9 optimization for three compounds, the amount of S9 was calibrated to a set amount of protein per plate (1.1 mg/plate). Secondly, the 10 test doses were placed in the initial, linear, nontoxic portion of the dose-response curves. The use of ten closely spaced, nontoxic doses allowed for a more accurate estimate of the slope.

Animals↗
PubMed1985

Dietary factors affecting the urinary mutagenicity assay system. II. The absence of mutagenic activity in human urine following consumption of red wine or grape juice.

The mutagenic activity of urine samples from nonsmoking individuals before and after the consumption of either red wine or grape juice was determined. Urine samples collected from individuals on liquid or regular diets were concentrated using XAD-2 resin. No mutagenic activity of urine concentrates was detected with Salmonella tester strains TA98 or TA100 with or without microsomal activation. The addition of 1000 units of beta-glucuronidase into the agar overlay did not show any mutagenic activity. The mutagens in red wine and grape juice, however, were extracted using the XAD-2 column. Concentrates of urine samples spiked with either of the two extracts exhibited mutagenic activity.

Diet↗
PubMed1988

Ames mutagenicity and concentration of the strong mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone and of its geometric isomer E-2-chloro-3-(dichloromethyl)-4-oxo-butenoic acid in chlorine-treated tap waters.

The Ames mutagenicity and the concentration of the strong Ames mutagen 3-chloro-4-(dichloro-methyl)-5-hydroxy-2(5H)-furanone (MX) and its geometric isomer E-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (E-MX), derived from chlorination of humus, were determined in XAD extracts of tap water collected from 26 localities in Finland. The 23 tap waters treated with disinfectants gave a positive response in strain TA100. MX and E-MX were detected in all extracts exhibiting mutagenicity with the exception of 3 extracts of marginal activity. MX accounted for 15-57% (average 33%) of the observed mutagenicity. The concentration of E-MX was slightly lower than the corresponding concentration of MX. Linear correlations were observed between mutagenicity and concentration of MX and E-MX, with correlation coefficients of 0.894 for MX and 0.910 for E-MX.

Chlorine↗
PubMed1993

Mutagenic activity of the methyl and phenyl derivatives of the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx) in the Ames test.

The mutagenic activity of 15 different mono-, di-, tri-, and tetramethyl derivatives of the food mutagen IQx (2-amino-3-methylimidazo[4,5-f]quinoxaline), one diphenyl derivative of IQx and two phenyl derivatives of 5-MeIQx (2-amino-3,5-dimethylimidazo[4,5-f]quinoxaline) were studied in the Ames test with Salmonella typhimurium TA98 and enzymatic activation (S9). The number and positioning of the methyl groups strongly affected the mutagenic activity. The phenylated compounds showed weak mutagenic potency. It seems that both resonance stabilization of the nitrenium ion and steric effects are important in determining mutagenic potency.

Animals↗
PubMedDate not supplied

Mutagens in larger fungi. II. The mutagenicity of commercial pickled Lactarius necator in the Salmonella assay.

In the course of an ongoing screening of larger mushrooms for the occurrence of chemical mutagens, 33 out of 48 species tested exhibited a significant direct mutagenic activity in the Salmonella/microsome assay (Sterner et al., 1982). (No mutagens requiring metabolic activation were indicated.) These findings are of some concern, since mushrooms are used extensively as food in many areas, and there are strong indications that carcinogens in food are of considerable importance in cancer aetiology (Sugimura, 1979). A recent communication by Knuutinen and von Wright (1982) on the mutagenicity of 4 Lactarius species collected in Finland prompts us to report our own results from mutagenicity tests with commercially preserved (pickled) Lactarius necator.

Basidiomycota↗
PubMed1992

Mechanism of mutagenicity by 5-hydroperoxymethyl-2'-deoxyuridine, an intermediate product of ionizing radiation, in bacteria. HPMdU bacterial mutagenicity and oxidation of DNA bases.

The specific objective was to find what processes are responsible for the mutagenicity of 5-hydroperoxymethyl-2'-deoxyuridine (HPMdU), which is a product of ionizing radiation, and what role transition metal ions play in those processes. We found that HPMdU is a more potent mutagen than its decomposition products 5-hydroxymethyl-2'-deoxyuridine (HMdU) and 5-formyl-2'-deoxyuridine (FdU) in the Salmonella typhimurium strains tested, with the TA100 strain being the most sensitive. HMdU exerted intermediate mutagenicity and FdU was the weakest of the three compounds. At 50 nmoles/plate, HPMdU increased the number of revertants by 4-fold, whereas 1000 nmoles HMdU was required to enhance the number of revertants by 5-fold. Pretreatment of TA100 with o-phenanthroline, a membrane-permeable Fe and Cu chelator, caused an increase in mutagenicity of the low HPMdU doses but inhibited that of the 50 nmoles HPMdU/plate, while desferal, a membrane-impermeable Fe chelator, had virtually no effect. Azide (a catalase inhibitor) enhanced HPMdU mutagenicity, whereas 3-amino-1,2,4-triazole (a catalase and peroxidase inhibitor) and ammonium formate (a hydroxyl radical scavenger) were protective. Preincubation of TA100 cells with 20 and 40 nM HPMdU caused dose-dependent formation of the oxidized DNA base derivatives HMdU, thymidine glycol and 8-hydroxyl-2'-deoxyguanosine (8-OHdG), known hydroxyl radical-mediated oxidation products. Cumulatively, these results suggest that the genetic effects of HPMdU are due to its hydroperoxide moiety, which upon reacting with Fe generates hydroxyl radicals that in turn oxidize neighboring bases in cellular DNA. This also may be a mechanism by which ionizing radiation exerts its long-term effects.

DNA Damage↗
PubMed1994

Todralazine influence upon the mutagenicity of some direct- and indirect-acting mutagens.

Todralazine decreased the mutagenic activity of tested direct- and indirect-acting mutagens. Despite the marked differences between efficient todralazine doses (ED50) it was observed that, in the case of tested indirect mutagens as well as in some of the direct mutagens, the decrease of mutagenicity by todralazine was very strong, exceeding 80% in some cases.

4-Nitroquinoline-1-oxide↗
PubMed2001

Mutagenicity of nitric oxide-releasing compounds in Escherichia coli: effect of superoxide generation and evidence for two mutagenic mechanisms.

The mutagenicity of three nitric oxide (NO) donors, 3-morpholinosydnonimine (SIN-1), a compound generating the precursors of peroxynitrite NO and superoxide, diethylamine/NO (DEA/NO) and spermine/NO (SPER/NO), both releasing authentic NO was analyzed using Escherichia coli tester strains IC203, carrying a deletion of the oxyR gene, and its oxyR(+) parent IC188 (the alternative name of WP2 uvrA/pKM101). The OxyR protein is a redox-sensitive transcriptional activator of genes encoding antioxidant enzymes. Strains IC203 and IC188 contain error-prone DNA polymerases polV, encoded by the chromosomal umuDC genes, and polRI, encoded by mucAB genes carried by pKM101. SIN-1 was determined to be an oxidative mutagen giving a positive response only in IC203, whereas DEA/NO and SPER/NO induced similar positive responses in IC203 and IC188 and were considered as non-oxidative mutagens. The spectrum of ochre suppressors in Trp(+) revertants induced by SIN-1 in IC203 was characterized by a higher number of TA-->AT transversions and GC-->AT transitions, and a lower number of GC-->TA transversions, with respect to the untreated control. The mutagenicity of SIN-1 in IC203, probably induced by peroxynitrite through reactive derivatives, was enhanced in the presence of plumbagin (PLB), a superoxide generator. Superoxide generation by PLB, as well as formation of peroxynitrite in cells treated with SIN-1, evaluated by monitoring the oxidation, respectively, of dihydroethidium and dihydrorhodamine 123, were greater in IC203 than in IC188. Formation of peroxynitrite in IC203 treated with SIN-1 was stimulated by PLB. After treatment with DEA/NO and SPER/NO the number of revertants scored in IC188 was higher than in strains IC187, containing only polV, and IC204, deficient in both polV and polRI. For these compounds, induced suppressor revertants in IC187 and IC204 were almost exclusively GC-->AT transitions, whereas in IC188 significant levels of GC-->TA and TA-->AT transversions were also induced. Mutagenesis by both DEA/NO and SPER/NO was partially inhibited in the presence of PLB. The results show the usefulness of the new tester strain IC203 to differentiate NO-promoted mutagenic mechanisms that involve or do not involve oxygen radicals.

DNA Damage↗
PubMed1999

Mutagenic activity of 2-phenylbenzotriazole derivatives related to a mutagen, PBTA-1, in river water.

A mutagen, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]5-ami no-7-bromo-4-chloro-2H-benzotriiazole (PBTA-1), isolated from water of the Nishitakase River in Kyoto exhibits potent mutagenic activity in Salmonella typhimurium TA98 with S9 mix and has characteristic moieties, including bromo, chloro, acetylamino, bis(2-methoxyethyl)amino and primary amino groups on a 2-phenylbenzotriazole skeleton. The mutagenicities of PBTA-1, its congeners and five related 2-phenylbenzotriazoles were examined in S. typhimurium TA98 with S9 mix in order to elucidate the structure-activity relationships. The data obtained suggest that a primary amino group plays an essential role in the mutagenic activity as do aromatic amines including heterocyclic amines in cooked foods. The effect of planarity of the 2-phenylbenzotriazole ring was significant, and in addition, halogen groups of PBTA-1 influenced the enhancement of the mutagenic activity.

Animals↗
PubMed1996

Intestinal mutagenicity of two carcinogenic food mutagens in transgenic mice: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and amino(alpha)carboline.

The heterocyclic amines produced during the cooking of meat, including amino(alpha)carboline (AalphaC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), are potent bacterial mutagens and are carcinogenic in rodents. PhIP is mutagenic in the small intestine, but its mutagenicity in the colon, where most human intestinal cancers arise, has not been reported, nor has the mutagenicity of AalphaC. In this study, AalphaC (800 p.p.m.) was fed for 30 and 45 days and PhIP (100 and 400 p.p.m.) was fed for 30, 60 and 90 days to groups of F1 (C57BL/6 x SWR) mice hemizygous for multiple tandem copies of a lacI transgene (the Big Blue mouse) and heterozygous at the endogenous Dlb-1 locus. The mutant frequencies were assayed at Dlb-1 and at lacI in the small intestine and at lacI in the colon. PhIP induced mutations at both loci in the small intestine and induced slightly fewer mutations in the colon. The accumulation of mutations at both loci appears to be linear with both PhIP concentration and duration of exposure and, thus, with dose (concentration x duration). The linear increase with time is in agreement with predictions about the effectiveness of chronic treatment protocols for tests of in vivo mutagenicity. Unlike PhIP, AalphaC induced mutations specifically in the colon and not in the small intestine, thereby showing a dramatic tissue specificity. The rate (mutations/p.p.m. day) was similar to PhIP.

Animals↗
PubMed1983

Studies on the efficiency of the Salmonella/rat hepatocyte assay for the detection of carcinogens as mutagens: activation of 1,2-dimethyl-hydrazine and procarbazine into bacterial mutagens.

Aflatoxin B1, benzo[a]pyrene, N-nitrosomorpholine, procarbazine (PC) and 1,2-dimethylhydrazine (DMH) were used to investigate the efficiency of the Salmonella/rat hepatocyte assay for detecting carcinogens as mutagens. In this assay, bacteria and the test compound were co-incubated with freshly isolated rat hepatocytes and then plated onto minimal glucose agar. Factors for optimal mutagenicity, including the number of hepatocytes and the number of bacteria, the type of assay medium and the length of incubation in liquid medium were investigated. All the compounds were metabolized into bacterial mutagens. Mediation of the mutagenicity of PC and DMH by rat hepatocytes indicates that freshly isolated cells of this type are a useful alternative metabolic activation system for use in screening chemicals found to be non-mutagenic in the Salmonella/microsome assay.

1,2-Dimethylhydrazine↗
PubMed1987

Mutagenic compounds in an extract from rutae herba (Ruta graveolens L.). I. Mutagenicity is partially caused by furoquinoline alkaloids.

Mutagenicity testing of a commercial extract from Rutae Herba (Tinctura Rutae) revealed a strong effect in Salmonella typhimurium strain TA98 without S9 mix. In the presence of S9 mix only a weak response was observed. Moderate mutagenic effects were detected with and without S9 mix using strain TA100. The extract used contained the furoquinoline alkaloids dictamnine, gamma-fagarine, skimmianine, pteleine and kokusaginine, as indicated by g.c. and g.c.-m.s. analysis. The pure compounds exhibited a mutagenic activity only in the presence of S9 mix in strain TA98 as well as in strain TA100, but their specific mutagenicity differed greatly in strain TA98. We conclude that the extract studied contains different mutagenic activities and that these are only partially due to the furoquinolines present in the extract.

Alkaloids↗
PubMed1988

Anti-mutagenicity of catechin against environmental mutagens.

Catechu is the non-mutagenic component of betel quid. We have tested catechu extract and catechin for anti-mutagenic activity in Salmonella typhimurium strain TA98 against environmental mutagens relevant to India. Catechu extract, as well as catechin, shows a dose-dependent decrease in the mutagenicity of tobacco and masheri extracts, and bidi and cigarette smoke condensates in TA98 with S9 mix. Mutagenicity of extracts of charred and non-charred meat in TA98 is also inhibited by catechu extract and catechin in a dose-dependent manner with or without S9 mix.

Animals↗