Mutagen activation by cDNA‐expressed P1450, P3450, and P450a

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Abstract
CDNAs for rodent P1450, P3450, and P450a were expressed in the modified vaccinia virus-T7 RNA polymerase system. Each P450 exhibited its appropriate molecular weight and characteristic enzyme activity. Aryl hydrocarbon hydroxylase activity was catalyzed by P1450, acetanilide hydroxylase by P3450, and testosterone 7a-hydroxylase by P450a. Ethoxycoumarin deethylase was exhibited by both P1450 and P3450. Each expressed P450 was also analyzed for its ability to activate 19 carcinogens of diverse classes to their mutagenic forms. Most notable was the activation of several polycyclic aromatic hydrocarbons by P1 and the activation of acetylaminofluorene, 4-aminobiphenyl, and several heterocyclic amine food pyrolysate products by P3450. P450a, in contrast, showed slight mutagen activation only toward N-hydroxy-2-acetyl aminofluorene. The vaccinia virus-T7 RNA polymerase system described here can express cDNAs for diverse forms of P450, each of which can then be characterized for substrate and product specificity and for mutagen activation.