Mutagenicity of some substituted 1-phenyl-3,3-dimethyltriazenes. II. Chromosomal aberrations in human peripheral lymphocytes in vitro

The chromosome-breaking activity of four 1-(phenyl)-3,3-dimethyltriazenes was tested in vitro on human peripheral blood lymphocytes using S9 mix as a metabolic activation system. 1-(4-Nitrophenyl)-3,3-dimethyltriazene was the most active compound. The difference in the frequency of chromosomal aberrations in a test with and without metabolic activation was significant at the 1% level of significance. The lowest frequency of chromosomal aberrations was induced by 1-(4-methylphenyl)-3,3-dimethyltriazene which, under the conditions of this experiment, is the least stable and probably rapidly degraded to non-active compounds. The chromosomal aberrations were also induced by 1-(4-chlorophenyl)-3,3-dimethyltriazene and 1-(4-bromophenyl)-3,3-dimethyltriazene, this activity was unrelated to metabolic activation.     

Mutagenicity of some substituted 1-phenyl-3,3-dimethyltriazenes: II. Chromosomal aberrations in human peripheral lymphocytes in vitro

The chromosome-breaking activity of four 1-(phenyl)-3,3-dimethyltriazenes was tested in vitro on human peripheral blood lymphocytes using S9 mix as a metabolic activation system. 1-(4-Nitrophenyl)-3,3-dimethyltriazene was the most active compound. The difference in the frequency of chromosomal aberrations in a test with and without metabolic activation was significant at the 1% level of significance. The lowest frequency of chromosomal aberrations was induced by 1-(4-methylphenyl)-3,3-dimethyltriazene which, under the conditions of this experiment, is the least stable and probably rapidly degraded to non-active compounds. The chromosomal aberrations were also induced by 1-(4-chlorophenyl)-3,3-dimethyltriazene and 1-(4-bromophenyl)-3,3-dimethyltriazene, this activity was unrelated to metabolic activation.     

Mutagenicity of bithionol sulfoxide and its metabolites in the salmonella/mammalian microsome test

The mutagenic effects of bithionol sulfoxide and its two major metabolites, bithionol and bithionol sulfone, on 4 Salmonella typhimurium strains (TA97, TA98, TA100 and TA102) were investigated. Bithionol sulfoxide was found to be mutagenic to TA98 and TA100. However, mutagenicity was abolished in the presence of rat-liver S9 fractions.     

Lack of mutagenicity of some phytoestrogens in the salmonella/mammalian microsome assay

8 phytoestrogens were tested for mutagenicity using a variation of the Salmonella/mammalian microsome (or Ames) assay. Zearalenone is a mycotoxin produced by a grain contaminant, Fusarium graminearum (Gibberella zeae) and the isomers of zearalanol are reduced derivatives of this compound. The remaining compounds are all flavonoids which occur naturally at relatively high concentrations in many plants, particularly legumes. 4 of these flavonoids (daidzein, genistein, formononetin and biochanin-a) are isoflavones and the 5th, coumestrol, is a coumestan. Each compound was tested at several concentrations ranging from 1--500 micrograms per plate. The microsomal fracton was obtained from Aroclor 1254 (a PCB)-induced rat livers. None of the compounds tested was mutagenic to Salmonella strains TA1538, TA98 or TA100 at any concentration.     

Mutagenicity of chloro-olefins in the Salmonella/mammalian microsome test. I. Allyl chloride mutagenicity re-examined

Contrary to findings published up to now, allyl chloride, a well known directly acting mutagen for Salmonella typhimurium, is efficiently activated by rat-liver homogenate (S9 mix) under non-standard mutagenicity testing conditions. Its indirect, S9-mediated mutagenic activity is greatly enhanced when longer than standard preincubation times are applied. The indirect mutagenicity of allyl chloride, thus revealed, greatly exceeds its direct mutagenic activity. Obviously, standard mutagenicity testing conditions cannot be regarded as reliable tools for the evaluation of the full genotoxic potential of allyl chloride and, possibly, of other related compounds.     

Mutagenicity of marijuana and Transkei tobacco smoke condensates in the salmonella/microsome assay

Extracts and smoke condensates of marijuana, Transkei home-grown tobacco and also commercial cigarette tobaccos were assayed for their mutagenic activity to Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538, both with and without metabolic activation. No mutagenic activity was detected in dichloromethane extracts of marijuana and tobacco per se, but all the smoke condensates exhibited mutagenicity with metabolic activation. The only strain not mutated by any of the pyrolyzates was TA1535. Transkei tobacco pyrolyzate proved to be the most mutagenic, followed by marijuana, pipe and cigarette tobacco. Mutagenicity was positively associated with the nitrogen content of the various products. The potent mutagenic action of marijuana smoke condensate, coupled with a condensate yield of more than 50% higher than that of cigarette and pipe tobacco, indicates a high carcinogenic risk associated with marijuana smoking.     

Mutagenicity of the coccidiostat diaveridine in the Salmonella/mammalian microsome assay

The coccidiostat diaveridine was tested for mutagenicity in the Salmonella/microsome assay with tester strains TA100 and TA98. This compound was not mutagenic in either tester strain in the presence and absence of rat S9 mix, but was found to be mutagenic in strain TA100 after metabolic activation with hamster S9 mix.     

Mutagenicity of the mycotoxin emodin in the salmonella/microsome system.

The mycotoxin emodin was found to be a frameshift mutagen for Salmonella typhimurium strain TA 1537 after metabolic activation in a mammalian microsome system.     

Mutagenicity of the mycotoxin emodin in the salmonella/microsome system.

The mycotoxin emodin was found to be a frameshift mutagen for Salmonella typhimurium strain TA 1537 after metabolic activation in a mammalian microsome system.     

Mutagenicity of N-nitrosodiethanolamine in the Salmonella/microsome test

Mutagenicity of a commercially available N-nitrosodiethanolamine (NDELA) and purified NDELA was examined, using Salmonella typhimurium TA100 as a tester strain. Purified NDELA was positive in the presence of liver activation system from either rats or hamsters, but the mutagenicity was completely lost when dimethyl sulfoxide (DMSO) was used as a solvent. In contrast, the commercial NDELA which was chemically of 93.8% purity showed positive mutagenicity without metabolic activation, and the liver activation system and DMSO had no effect on the direct mutagenic activity. These results indicate that an apparent discrepancy among previous findings of several investigators with the mutagenic response of NDELA might be due to an impurity in NDELA samples and the solvent, DMSO.     

Mutagenicity studies on coffee. The influence of different factors on the mutagenic activity in the Salmonella/mammalian microsome assay

Recently, mutagenic activity on several strains of Salmonella typhimurium has been found in many heat-processed foodstuffs. The previously reported direct-acting mutagenic activity of coffee in Salmonella typhimurium TA100 (Ames assay) was confirmed in our study. In addition to TA100, a mutagenic effect of coffee was also found by using the newly developed strain TA102. The mutagenic activity was abolished by the addition of rat-liver homogenate. 10% S9 mix completely eliminated the mutagenic activity of 30 mg of coffee per plate. The addition of reduced glutathione to active S9 further decreased the mutagenic activity and also reduced the mutagenicity together with inactivated S9. The compound or compounds responsible for this inactivation are heat-labile and seem to be located in the cytosol fraction of the S9. Part of the mutagenicity of coffee was also lost spontaneously upon incubation at temperatures between 0 degrees and 50 degrees C. The loss of activity was dependent on temperature, being more pronounced at 50 degrees C compared to 0 degrees C (at 50 degrees C approximately 50% of the mutagenic activity was lost after 6 h). As anaerobic conditions prevented this loss of mutagenicity almost totally, oxidative processes are probably responsible for the inactivation. The stability of the mutagen was not influenced by incubation at low pH values (pH 1-3), with or without the addition of pepsinogen. The mutagenic properties of methylglyoxal, which to some extent could be responsible for the mutagenic activity of coffee, were compared with those of coffee. Methylglyoxal was strongly mutagenic towards Salmonella typhimurium TA100 and TA102. Its mutagenic activity was partially inactivated by the addition of 10% S9. Glyoxalase I and II together with reduced glutathione abolished the mutagenic activity of methylglyoxal but reduced the mutagenicity of coffee by only 80%. Since these enzymes occur in mammalian cells, the mutagenic compound(s) of coffee could also be degraded in vivo. This conclusion is supported by the fact that a long-term carcinogenicity study with rats was negative. These results clearly demonstrate that the effects observed in vitro do not necessarily also occur in vivo, but that in vitro experiments may contribute to the understanding of fundamental mechanisms of chemical carcinogenesis.     

Mutagenicity of pyrrolizidine alkaloids in the Salmonella typhimurium/mammalian microsome system.

The mutagenicity of a series of pyrrolizidine alkaloids, and of extracts from several Italian Senecio species containing pyrrolizidine alkaloids, including S. inaequidens, S. fuchsii and S. cacaliaster, were tested using the Salmonella typhimurium/mammalian microsome system. Retrorsine, senecivernine, seneciphylline and the Senecio extracts showed a weakly mutagenic activity.     

Mutagenicity of wood smoke condensates in the Salmonella/microsome assay

Smoke condensates of woods used for food preservation and aromatization in Nigeria were tested for mutagenic activity using Salmonella typhimurium TA98 and TA100. The woods were: white mangrove (Avicennia nitida), red mangrove (Rhizophora racemosa), mahogany Khaya sp.), abura (Mitragyna ciliata), alstonia (Alstonia boonei) and black afara (Terminalia ivorensis). Cigarette tar was tested for comparison. The condensates induced dose-dependent increases in the number of His+ revertants mainly with S9 mix. With the exception of mahogany and cigarette smoke condensate, the smoke condensates induced more revertants/microgram condensate in TA100 than in TA98. The number of revertants/microgram condensate ranged between 0.04 and 0.9 for the wood smoke condensates and was 0.12 for the cigarette smoke in TA100. The range was between 0.1 and 0.30 for the wood smoke condensates and 0.18 revertants/microgram condensate for cigarette smoke condensate in TA98. Concentrations of 7 polycyclic aromatic hydrocarbons (PAHs) in the condensates were determined namely, pyrene, benzo[a]pyrene, benz[a]anthracene, benzo[k]fluoranthene, benzo[b]chrysene, benzo[g,h,i]perylene and dibenzo[a,e]pyrene. The condensates contained varying concentrations of the individual PAHs and those with higher concentrations generally showed greater mutagenic activities. However, the order of mutagenic potency in the bacterial strains differed from the order of PAH concentrations, which were lower than the concentrations at which they are reported to induce mutations. When 6 of the PAHs were mixed in the concentrations in which they were found in the individual condensates, the mixtures did not induce mutation so that the contribution of the PAHs to the mutagenic activities of the condensates could not be determined.     

Mutagenicity of pyrrolizidine alkaloids in the Salmonella typhimurium/mammalian microsome system

The mutagenicity of a series of pyrrolizidine alkaloids, and of extracts from several Italian Senecio species containing pyrrolizidine alkaloids, including S. inaequidens, S. fuchsii and S. cacaliaster, were tested using the Salmonella typhimurium/mammalian microsome system. Retrorsine, senecivernine, seneciphylline and the Senecio extracts showed a weakly mutagenic activity.