P450 IN THE RAT AND MAN - METHODS OF INVESTIGATION, SUBSTRATE SPECIFICITIES AND RELEVANCE TO CANCER

1. Considerable evidence has been accumulated that orthologous rat and human P450 forms oxidize numerous chemicals in a highly similar manne r, including the detoxication and activation of mutagens and carcinoge ns. 2. Nevertheless, certain specific substrates of rat P450s are not so well oxidized by the orthologous human forms, and vice versa. 3. Ce rtain mutagens and carcinogens can be activated in a similar way by di fferent (non-orthologous) forms in rat and man, confirming that studie s on animals, directed ultimately to man, can be indicative but not pr edicative of chemical mutagenesis and carcinogenesis.