Carcinogenesis benzopyrene

In five of six nondietary tumor-promotion experiments, sodium selenide significantly reduced the number of mice with tumors induced by 7,12-dimethyl-benzanthracene (DMBA)-croton oil (1). In these experiments, sodium selenide was applied concomitantly along with croton oil to female Swiss albino mice initiated with DMBA. Riley has also observed a reduction in DMBA-phorbol ester carcinogenesis by sodium selenide (2). The effect of selenium-deficient and selenium-adequate diets on DMBA-croton oil and benzopyrene skin carcinogenesis has also been studied. Supplemental dietary selenium inhibited both types of carcinogenesis. 

Figure 2.27. Mutagenesis and carcinogenesis by benzopyrene metabolites. The hydrocarbon, which is inert by itself, is converted by cytochrome P450 lAl to the nltimate carcino-gen 7,8-dihydroxy-9, lO-epoxy-7,8,9,10-tetrahydrobenzopyrene. This intercalates into and reacts with DNA, which canses mnta-tions and may lead to cancer. The compoimd may also be conjn-gated (and thereby detoxified) by conjngationto glntathione.

Wynder EL, Ritz LFN. 1957. Effect of concentrations of benzopyrene in skin carcinogenesis. J Natl Cancer Inst 19 361-370. 

Roe, F.J.C. Role of 3,4-benzopyrene in carcinogenesis by tobacco smoke condensate Acta Unio Intemat. Contra Cancrum 19 (1963) 730. 

Wynder, E.L. Some concepts of the less harmful cigarette in A safe cigarette Banbury Report 3, edited by G.B. Gori and EG. Bock, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (1980) 3-12. Wynder, E.L., L. Fritz, and N. Furth Effect of concentration of benzopyrene in skin carcinogenesis J. Natl. Cancer Inst. 19 (1957) 361-370. 

We are aware too that genetics can play a role in susceptibility. Should one therefore select a sensitive animal model or a resistant one For example, for skin carcinogenesis, the SENCAR mouse is regarded as extremely sensitive to many carcinogens, in particular polycyclic aromatic hydrocarbons. On the other hand, C57 Black mice are insensitive to benzopyrene as an initiator. 

Colburn and Boutwell [206] concluded that at least there does seem to be a positive correlation of tumorigenesis with one or both of the nucleic acids DNA and RNA. Very recently, it was stated that the critical experiments have yet to be done to ascertain which (if any) of the macromolecules to which hydrocarbons (or their expoxides) bind is the primary target that triggers the carcinogenic process [139]. From quantitative structure-activity analysis, Franke [207] suggests that microsomal arylhydrocarbon benzopyrene hydroxylase may be the first step in chemical carcinogenesis of polycyclic hydrocarbons. 

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