Tumor initiation by 7,12-dimethylbenz[a]anthracene in dermal melanocytes of hamster: inhibition through 7,8-benzoflavone.
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 weight) and melanoma development pursued with or without subsequent promotion through repeated topical administration of 12-O-tetradecanoylphorbol-13-acetate (40 nmol/animal, 3 X weekly). A single intragastric application of BF (200 mg/kg body weight) 2 h prior to DMBA resulted in a suppression of melanoma yields by approximately 70%. Further, there were indications that BF generally causes a decrease of melanoma rates and an increase of survival rates. The study provides a first mechanistic concept for melanoma initiation by DMBA. It shows that metabolic activation of DMBA (i) is prerequisite to initiation and (ii) has a similar molecular basis as in other target cells of DMBA, the essential pathway including the cytochrome P-448-dependent monooxygenase system.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001551:Benz(a)Anthracenes / Q000037:antagonists & inhibitors*; D001571:Benzoflavones / Q000494:pharmacology*; D006224:Cricetinae; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D008544:Melanocytes / Q000187:drug effects*; D008647:Mesocricetus; D009374:Neoplasms, Experimental / Q000139:chemically induced; D012878:Skin Neoplasms / Q000139:chemically induced*; D013997:Time Factors
D001551:Benz(a)Anthracenes; D001571:Benzoflavones; D005419:Flavonoids; D015127:9,10-Dimethyl-1,2-benzanthracene; C011512:alpha-naphthoflavone