The metabolic activation of 4,4'-methylene-bis-(2-chlorobenzeneamine) to a bacterial mutagen by hepatic postmitochondrial supernatant from human and other species.
4,4'-Methylene-bis-(2-chlorobenzeneamine) (MbOCA) is a commercially important industrial chemical that is carcinogenic in three animal species and mutagenic in the Ames test. The ability of hepatic postmitochondrial supernatant from humans, dogs, mice, and rats to activate MbOCA to a bacterial mutagen has been investigated using the Ames plate incorporation test and a bacterial fluctuation test. In the Ames plate test, hepatic S9 preparations from mice and Aroclor 1254-induced rats only were sufficiently active to produce a significant mutagenic response. Preincubation of MbOCA with S9 from human liver produced a slight increase in the number of revertants but not a doubling as compared to controls. However, using the more sensitive bacterial fluctuation test, liver S9 from all species activated MbOCA to a bacterial mutagen. The responses produced were dose-related and, for at least part of the dose range, were double the background levels observed in controls. The increases in the mutagenicity of MbOCA produced by liver S9 from humans, dogs, and rats were significant at the 0.1% level of probability. Liver S9 preparations from all species in which MbOCA is carcinogenic have now been demonstrated to be capable of activating this compound to a bacterial mutagen. The finding that S9 from human liver can also activate MbOCA to a mutagen increases the concern that it may be a human carcinogen.
D000818:Animals; D001559:Benzhydryl Compounds / Q000378:metabolism*; D001711:Biotransformation; D004285:Dogs; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008753:Methylenebis(chloroaniline) / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D013045:Species Specificity
D001559:Benzhydryl Compounds; D008753:Methylenebis(chloroaniline)