Polycyclic aromatic hydrocarbons and possible metabolites: convertogenic activity in yeast and tumor initiating activity in mouse skin

多环芳烃及其可能的代谢产物:在酵母中的转化活性和在小鼠皮肤中的肿瘤起始活性

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Abstract

The diploid respiratory-deficient strain of yeast D4-RDII was used to assay PAH and urethane as well as some oxygenated derivatives of PAH and the (aliphatic) epoxide hydrolase inhibitor TCPO for convertogenic (mutagenic) activity. As a positive control, the convertogenic ultimate rat liver carcinogen NOAcAAF was used. PAH and urethane were found inactive as convertogens, TCPO was weakly active, whereas oxygenated electrophilic derivatives of PAH, such as K-region oxides, were found strong convertogens. For comparison, some convertogenic key compounds were assayed for their tumor-initiating activity in mouse skin in the standardized system using TPA as a promotor. PAH were stronger initiators than all oxygenated derivatives of PAH tested. TCPO alone exhibited very weak, if any, initiating activity. It was unable to modify initiation to any significant extent, if administered 5 min prior to administration of an initiator. In the absence of correlation between convertogenic and initiating activity the question of the chemical nature of "ultimate initiators" of mouse skin carcinogenesis awaits further investigation.

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