A human cytochrome P-450 (P450) IBI cDNA was expressed in Sat-- charomyces cerevisiae, and the microsomes containing P450 IBI were used to examine the selectivity of this enzyme in the activation of a variety of environmental carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002 or NM2009 tester strains, using the SOS response as an end point of DNA damage. We also determined and compared these activities of P450 IBI with those catalyzed by recombinant human P450s 1A1 and 1A2, which were purified from membranes of Escherichia coli. The carcinogenic chemicals tested included 27 polycyclic aromatic hydro carbons and their dihydrodiol derivatives, 17 heterocyclic and aryl amines and aminoazo dyes, three mycotoxins, two nitroaromatic hydrocarbons, iV-nitrosodimethylamine, vinyl carbamate, and acrylonitrile. Among the three P450 enzymes examined here, P450 IBI was found to have the highest catalytic activities for the activation of ll,12-dihydroxy-ll,12- dihydrodibenzo(a,/)pyrene, l,2-dihydroxy-l,2-dihydro-5-methylchrysene, (+)-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, ll,12-dihydroxy-ll,12-di- hydrobenzo(g)chrysene, 3,4-dihydroxy-3,4-dihydrobenzo(c)phenanthrene, 3-amino-l,4-dimcthyl-5/f-pyrido|4,3-A)mdole. 2-aminoanthracene, 3-meth- oxy-4-aminoazobenzene, and 2-nitropyrene. P450 IBI also catalyzed the activation of 2-amino-3,5-dirnethylimidazo(4,5-/)quinoline, 2-amino-3,K-di- mothyliniida/o(4,5-/)(|uinoxaline. 2-amino-3-methyUmidazo(4^-/|quinoline, 2-aminofluorene, 6-aminochrysene and its 1^-dihydrodiol, (â€")-7,8-dihy- drtixy-7,8-dihydrohenzo|«Jpyreiie, l,2-dihydroxy-l,2-dihydroohrysene, 1,2- diliydroxy-1.2-dihydro-5.6-dimi'thylchrysene. 2,3-dihydroxy-2,3-dihydroflu- oranthene, 3,4-dihydroxy-3,4-dihydro-7,12-dimethylhenz(a)anthracene, and 6-nitrochrysene to appreciable extents. However, P450 IBI did not produce genotoxic products from benzo(a)pyrene, irans-3,4-dihydroxy-3,4-dihydro- benzo(a)anthracene,