Mutagenicity and chromosomal aberrations as an analytical tool for in vitro detection of mammalian enzyme-mediated formation of reactive metabolites.
1. Incubation of trichloroethylene, 1,1-dichloroethylene, vinylchloride, tetra-chlorocyclopentadiene, the nitroso derivatives of the pesticides Carbaryl, Prometryn, and Dodin in the presence of metabolically active mouse liver microsomes and bacteria as target cells were mutagenic, whereas tetrachloroethylene, 1,2 cis- and transdichloroethylene, hexachlorocyclopentadiene, carbontetrachloride, chloroform, halothane, trichlorofluoromethane and styrene were not activated to mutagenic species. 2. In a similar in vitro test system using freshly isolated human lymphocytes as target cells dimethylnitrosamine induced chromosomal aberrations. 3. It is concluded from the experiments that submammalian or mammalian in vitro cell systems with metabolically active liver microsomes are not only suitable to screen for chemical mutagens but to demonstrate formation of reactive intermediates, which are short lived and cannot be detected by chemical procedure.
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D012721:Carbaryl / Q000378:metabolism / Q000633:toxicity; D002869:Chromosome Aberrations; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006221:Halothane / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism / Q000633:toxicity; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D009603:Nitroso Compounds / Q000378:metabolism / Q000633:toxicity; D013343:Styrenes / Q000378:metabolism / Q000633:toxicity; D014116:Toxicology / Q000379:methods*
D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; D009603:Nitroso Compounds; D013343:Styrenes; D012721:Carbaryl; D006221:Halothane