The effects of benzoflavones on polycyclic hydrocarbon metabolism and skin tumor initiation.
The effects of benzoflavones on skin tumor initiation by polycyclic hydrocarbons and epidermal aryl hydrocarbon hydroxylase were investigated. 7,8-Benzoflavone (7,8-BF) was found to be a potent inhibitor of the inhibition of skin tumors by 3-methylcholanthrene (MC) as well as 7,12-dimethylbenz(a)anthracene (DMBA). 5,6-Benzoflavone(5,6-BF) inhibited tumor initiation by MC and DMBA, but to a lesser degree than 7,8-BF. Dose-response studies of the capacity of 7,8-BF to inhibit DMBA tumor initiation revealed that 7,8-BF was an effective inhibitor at 2.5 microgram and a maximum inhibition of 90% occurred at 100 microgram of 7,8-FB. The tumor initiating ability of 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHMe-12MeBA) was not inhibited by 7,8-BF. Epidermal aryl hydrocarbon(benzo(a)pyrene hydroxylase(AHH) was increased by 5,6-BF and either had no effect or was slightly inhibited by 7,8-BF when given either topically or i.p. Both flavones when added directly to the assay tubes inhibited the in vitro epidermal AHH activity from control and MC pretreated mice by greater than 75%. When added in vitro, 7,8-BF and 5,6-BF inhibited epidermally mediated covalent binding of radioactive DMBA and dibenz(a,h)anthracene to DNA by 50% or more. The inhibition of skin tumor initiation by 7,8-BF and 5,6-BF appears to be partially related to its ability to inhibit the formation of electrophilic intermediates.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D002277:Carcinoma / Q000139:chemically induced / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D008748:Methylcholanthrene / Q000378:metabolism*; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology
D001551:Benz(a)Anthracenes; D005419:Flavonoids; D013739:Testosterone; D004958:Estradiol; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D001579:Benzopyrene Hydroxylase; D010634:Phenobarbital