Metabolic activation and deactivation of mutagens and carcinogens.
The activity of some mutagens has been investigated in the Salmonella test either in the absence or in the presence of fortified rat liver microsomal fractions, together with an NADPH-generating system. With respect to their metabolic reactivity, the compounds tested could be distinguished according to four reproducible trends: (a) conversion of inert compounds into mutagenic metabolites (e.g. 2-aminofluorene and benzo(a)pyrene); (b) further enhancement of mutagenicity (e.g. 1,2-epoxybutane); (c) no effect on mutagenicity (e.g. glycidol, folpet, nitrofurantoin and 2-nitronaphtalene); (d) slight decrease (e.g. 1,1,1-trichlor 2,3-propenoxide), marked decrease (e.g. sodium nitrite, 5-nitro-2-furoic acid and captan) or even complete reversal of mutagenicity (e.g. styrene oxide, sodium azide, sodium dichromate and other Cr6+ compounds). The Salmonella/microsome test was effective in discriminating not only the mutagenic activity but also the metabolic reactivity of structurally related chemicals (e.g. the fungicides captan and folpet). In some cases, mutagens were tested also in the presence of other biological preparations (e.g. rat muscle or lung microsomal preparations, human gastric juice, serum, plasma or erythrocyte lysates). The mutagenic and metabolic properties of largely used products (e.g. an antibacterial drug containing nitrofurantoin and laboratory reagents containing sodium azide) have been also checked. The mechanisms underlying the metabolic behaviour of some of the mutagens tested have been reported. The results obtained have been correlated with the literature data on their carcinogenicity. Although these in vitro findings are only indicative of the possible metabolic fate of mutagens in the whole organism, the observed effects may be useful in order to explain the epidemiological data and the results of animal tests, and to assess the possible health hazards of mutagens.
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism* / Q000494:pharmacology; D009154:Mutation / Q000187:drug effects; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
D002273:Carcinogens; D009153:Mutagens