The role of cytochrome P-450 forms in 2-aminoanthracene and benz[alpha]pyrene mutagenesis. |
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Authors: | R L Norman U Muller-Eberhard E F Johnson |
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Institution: | Department of Biochemistry Scripps Clinic and Research Foundation La Jolla, California 92037 USA |
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Abstract: | The role of four forms of cytochrome P-450 from rabbit liver in the metabolic activation of two suspected carcinogens, 2-aminoanthracene and benzα]pyrene, was investigated with a S. typhimurium tester strain, TA 98. Each of the forms, 2,3,4 and 6 was reconstituted with NADPH-cytochrome P-450 reductase and lipid, and assay conditions were established such that the cytochrome P-450 concentration was rate-limiting. Under these conditions, cytochrome P-450 form 4, but not the other forms, converted 2-aminoanthracene into a potent mutagen. In contrast, form 6 was the only form which metabolized benzα]pyrene to a mutagen. These results indicate that specific cytochrome P-450 forms preferentially activate particular mutagens. |
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