US EPA

5144610 

Journal Article 

Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1 

Shimada, T; Hayes, CL; Yamazaki, H; Amin, S; Hecht, SS; Guengerich, FP; Sutter, TR 

1996 

Yes 

Cancer Research
ISSN: 0008-5472
EISSN: 1538-7445 

56 

13 

2979-2984 

English 

BIOSIS COPYRIGHT: BIOL ABS. A human cytochrome P450 (P450) 1B1 cDNA was expressed in Saccharomyces cerevisiae, and the microsomes containing P450 1B1 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 1B1 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 hydrocarbons and their dihydrodiol derivatives, 17 heterocyclic and aryl amines and aminoazo dyes, three mycotoxins, two nitroaromatic hydrocarbons, N-nitrosodimethylamine, vinyl carbamate, and acrylonitrile. Among the three P450 enzymes examined here, P450 1B1 was found to have the highest catalytic activities for the activation of 11,12-dihydroxy-11,12-dihydrodibenzo