Benzo alpyrene

Kurelec, B., Matijasevic, Z., Rijavec, M., Alacevic, M., Britvid, S., Muller, W.E.G., and Zahn, R.K. (1979). Induction of benzo[alpyrene monooxygenase in fish and the Salmonella test as a tool for detecting-mutagenic/carcinogenic xenobiotics in the aquatic environment, Bull Environ. Contam. Ibxicol. 21, 799. 

It is postulated that this ultimate carcinogen reacts covalently with nucleic acids, producing nucleic acid adducts. It has been demonstrated that benzo[a]pyrene reacts covalently with nucleic acids in vitro, provided that the microsomal enzyme systems necessary for activation are present, and also in whole cell systems. The 7,8-dihydrodiol metabolite of benzo [alpyrene binds more extensively to DNA after microsomal enzyme activation than does benzo [alpyrene or other benzolalpyrene metabolites, and the nucleoside adducts formed from the 7,8-dihydrodiol of benzolalpyrene are similar to those obtained from cells in culture exposed to benzolalpyrene itself. Furthermore, the synthetic 7,8-diol-9,10-epoxides of benzo [alpyrene are highly mutagenic in mammalian as well as in bacterial cells. 

The metabolite responsible for the carcinogenicity of benzo[a]pyrene (i.e., the ultimate carcinogenic metabolite) is the 7,8-dihydrodio 1-9,10-oxide. Some of the evidence is as follows the 7,8-dihydrodiol metabolite of benzo[a]pyrene binds more extensively to DNA after microsomal enzyme activation than other metabolites or benzo[alpyrene itself the nucleoside adducts formed are similar to those formed from benzo [a] pyrene itself the synthetic 7,8-dihydrodiol 9,10-oxides are highly mutagenic the 7,8-dihydrodiol is carcinogenic whereas the 4,5- and 9,10-epoxides are not. 

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