Effects of 7, 8-benzoflavone on skin tumor-initiating activities of various 7- and 12-substituted derivatives of 7, 12-dimenthylbenz[a]anthracene in mice

The skin tumor-initiating activities of various 7- and 12-substituted derivatives of 7, 12-dimethylbenz[a]anthracene (dmba) were investigated in female outbred charles river cd-1 mice. 7-formyl-12-methylbenz[a]anthracene (7-cho-12-mba) at 740 nmoles/mouse was an effective tumor initiator, at a dose 74fold greater than that of dmba. 7, 8-benzoflavone (7, 8-bf) inhibited the tumor-initiating activity of 7-cho-12-mba by 51%. 12-formyl-7-methylbenz[a]anthracene and 7, 12-diformylbenz[a]- anthracene, applied at initiating doses of 740 nmoles and 704 nmoles/mouse, respectively, were much less active than 7-cho- 12-mba. 7-bromomethyl-12-methylbenz[a]anthracene (7-brme- 12-mba) and 7-bromomethylbenz[a]anthracene (7-brmeba) were also investigated. 7-brme-12-mba was a more effective tumor initiator than 7-brmeba, but both were less active than dmba. 7, 8-bf inhibited the tumor-initiating activity of 7-brme- 12-mba and 7-brmeba by 34 and 54%, respectively. 12- bromomethyl-7-methylbenz[a]anthracene (12-brme-7-mba) was as active an initiator as 7-brme-12-mba. 7, 8-bf inhibited tumor initiation with 12-brme-7-mba by 29%. three naturally occurring flavones, quercetin, myricetin, and 4', 5, 7-trihydroxy- flavonone, and the cytochrome p450; inhibitor 1-benzylimidazole were investigated after topical application (100 µg) for their effects on tumor initiation with dmba. quercetin inhibited tumor initiation with dmba by 22%, whereas myricetin and 4', 5, 7- trihydroxyflavanone enhanced tumor initiation with dmba by 54 and 29%, respectively. 1-benzylimidazole had no effect. the abilities of the flavones and 1-benzylimidazole to inhibit aryl hydrocarbon hydroxylase in vitro did not correlate with their effects on tumor initiation with dmba.-j natl cancer inst 61: 135-140, 1978.