Tumor initiation by 7,12-dimethylbenz[a]anthracene in dermal melanocytes of hamster: inhibition through 7,8-benzoflavone

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Abstract
Initiation of dermal melanocytes by 7,12-dimethylbenz[a]-anthracene (DMBA) in the dorsal skin of Syrian golden hamsters was investigated for its sensitivity to inhibition by 7,8-benzoflavone (BF). Initiation was carried out by a single intragastric application of DMBA (50 mg/kg body wt) and melanoma development pursued with or without subsequent promotion through repeated topical administration of 12-O-tetradecanoylphorbol-13-acetate (40 nmol/animal, 3 .times. weekly). A single intragastric application of BF (200 mg/kg body wt) 2 h prior to DMBA resulted in a suppression of melanoma yields by .apprx. 70%. There were indications that BF generally causes a decrease of melanoma rates and an increase of survival rates. The 1st mechanistic concept is provided for melanoma initiation by DMBA. Metabolic activation of DMBA it prerequisite to initiation and has a similar molecular basis as in other target cells of DMBA, the essential pathway including the cytochrome P-488-dependent monooxygenase system.