Mutagenicity and Cytotoxicity of Benzo(A)Pyrene Arene Oxides, Phenols, Quinones, and Dihydrodiols in Bacterial and Mammalian Cells

Abstract

Twenty-nine benzo(a)pyrene derivatives were tested for mutagenic activity without metabolic activation in Salmonella typhimurium strains TA98, TA100, and TA1538 and in Chinese hamster V79 cells. The compounds studied included 4 arene oxides, all 12 isomeric phenols, 5 quinones, and 8 dihydrodiols. Benzo(a)pyrene 4,5-oxide was the most mutagenic of the compounds tested in both the bacterial and mammalian systems. The other arene oxides [benzo(a)pyrene 7,8-, 9,10-, and 11,12-oxides] were only weakly mutagenic in the S. typhimurium strains. However, in Chinese hamster V79 cells, benzo(a)pyrene 11,12-oxide was as potent a mutagen as was benzo(a)pyrene 4,5-oxide. Among the phenols, 6-hydroxybenzo(a)pyrene and 12-hydroxybenzo(a)pyrene were moderately mutagenic in strain TA98 of S. typhimurium, and 6-hydroxybenzo(a)pyrene was moderately mutagenic in V79 cells. The other 10 phenols, 5 quinones [benzo(a)pyrene 1,6-, 3,6-, 4,5-, 6,12-, and 11,12-quinones] and 8 dihydrodiols [benzo(a)pyrene cis-4,5-, trans-4,5-, cis-7,8-, trans-7,8-, cis-9,10-, trans-9,10-, cis-11.12-, and trans-11,12-dihydrodiols] were either inactive or only weakly mutagenic. 1-Hydroxybenzo(a)pyrene and 3-hydroxybenzo(a)pyrene were weakly mutagenic in strain TA98 of S. typhimurium, and benzo(a)pyrene 7,8-dihydro-diol was weakly mutagenic in V79 cells. Benzo(a)pyrene 11,12-quinone was extremely cytotoxic to the V79 cells but had no observable toxicity in the bacterial strains. © 1976, American Association for Cancer Research. All rights reserved.