Interspecies homology of cytochrome P-450: toxicological significance of cytochrome P-450 cross-reactive with anti-rat P-448-H antibodies in liver microsomes from dogs, monkeys and humans

The mutagenic activation of various promutagens by liver microsomes from dogs, monkeys and humans was investigated. Dog liver microsomes efficiently catalyzed the mutagenic activation of Trp-P-2 and Glu-P-1 followed by IQ and AAF. Monkey liver microsomes were most active in the activation of IQ followed by Glu-P-1, AAF and Trp-P-2. Although there were remarkable individual differences, human liver microsomes were found to be most active in the mutagenic activation of IQ followed by Trp-P-2, Glu-P-1 and AAF. Antibodies against rat P-448-H inhibited the mutagenic activation of Glu-P-1, Trp-P-2 and IQ in rat and dog liver microsomes, and Glu-P-1 and Trp-P-2 in monkey liver microsomes. The activation of Glu-P-1 and IQ in human liver microsomes was also strongly inhibited by anti-P-448-H antibodies. The amounts of cytochrome P-450 cross-reactive with anti-P-448-H antibodies in human liver microsomes highly correlated with the capacity to activate Glu-P-1, Trp-P-2 and IQ but not AAF.