Benzo pyrene carcinogenic activity

Table II. Carcinogenic Activities of Benzo[a]pyrene (BP) Metabolites...

Recent structure-activity studies of 1-alkylbenzo[a]pyrenes also suggest that DNA intercalation of benzo[a]pyrene (BP) metabolites plays a role in the mechanism of BP carcinogenesis (38). The addition of bulky alkyl groups at the 1-position of BP, which inhibit DNA intercalation of 1-alkyl-BP metabolites (19), causes a reduction in carcinogenic activity. 

The low-molecular weight hydrocarbons (mol wt <216) are regarded as non-carcinogenic, unlike many heavy PAHs. Furthermore, the degree of carcinogenic activity depends on the structure of the compound. The maximum limits for PAH concentration in air and water samples, therefore, have been established for individual PAHs. Benzo[a]pyrene (BaP, Figure 13.16) is... 

Continued studies from several laboratories of the binding, mutagenicity and tumorigenicity of benzo [a] pyrene and its derivatives led to the identification of (+)-(7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[aJpyrene (a diol epoxide-2 diastereomer) as the principal metabolite responsible for the carcinogenic activity of benzo[a]pyrene. Only one of the four metabolically possible isomers of the 7,8-diol-9,10-epoxide was found to have high tumorigenic activity... 

Rossi L, Barbieri 0, Sanguineti M, et al. 1983. Carcinogenic activity of benzo(a)pyrene and some of its synthetic derivatives by direct injection into the mouse fetus. Carcinogenesis 4 153-156. 

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[ ]pyrene binds more extensively to DNA after microsomal enzyme activation than does benzo[a]pyrene or other benzo[a]pyrene metabolites, and the nucleoside adducts formed from the 7,8-dihydrodiol of benzo[tf]pyrene are similar to those obtained from cells in culture exposed to benzo[ ]pyrene itself. Furthermore, the synthetic 7,8-diol-9,10-epoxides of benzo[a]pyrene are highly mutagenic in mammalian as well as in bacterial cells. 

It shows DNA damaged by the environmental chemical carcinogen benzo[ ]pyrene in the active site of the human DNA bypass polymerase k. 

The polycyclic aromatic hydrocarbon carcinogens, which are very ubiquitous, are metabolized by the microsomal mixed-function oxidase system of target tissues to a variety of metabolites such as phenols, quinones, epoxides, dihydrodiols and dihydrodiol-epoxides ( ). The mqjor pathway of activation of benzo(a)pyrene (BP) leads to the formation of dihydrodiol-epoxide of BP which interacts predominantly with the 2-amino of guanine of DNA. The dihydrodiol-epoxide of BP appears to be the major ultimate electrophilic, mutagenic, and carcinogenic metabolite of BP ( ). Nevertheless, other metabolites such as certain phenols, epoxides and quinones may contribute to the overall carcinogenic activity of BP. In addition, a free radical mechanism may also be partly involved in its carcinogenic activity. 

As early as the mid-1950s, Wynder and Wright (4353) noted that the concentration of B[a]P in CSC was insnfficient to acconnt for its observed carcinogenicity to monse epidermis The concentration in which benzo[a]pyrene seems to be in cigarette tar is insnfficient to acconnt for the observed carcinogenic activity to monse epidermis. ... 

In non-CSC-related studies, Warshawsky et al. (26A180) found in their study of the carcinogenic potential of mixtures that the carcinogenic activity of a mixture cannot be accounted for by the level of benzo[a]pyrene present. ... 

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