Effects of benzoflavones and trichloropropene oxide on aryl hydrocarbon hydroxylase activity and initiation of skin tumors

7,8 Benzoflavone (7,8 BF) inhibited the initiation of skin tumors by 3 methylcholanthrene (MC) and 7,12 dimethylbenz(a) anthracene (DMBA). 5,6 Benzoflavone (5,6 BF) also inhibited tumor initiation by MC and DMBA but to a lesser degree. Dose response studies of the capacity of 7,8 BF to inhibit tumor initiation by DMBA revealed that 7,8 BF was an effective inhibitor at concentrations equivalent to that of DMBA and a maximum inhibition was observed at 20 times that of DMBA. Epidermal aryl hydrocarbon dydroxylase was increased by 5,6 BF and inhibited by 7,8 BF when given either topically or i.p. When added in vitro 7,8 BF inhibited epidermal NADPH dependent covalent binding of tritiated MC to DNA by 50%. Trichloropropene oxide (TCPO) only slightly increased the in vitro covalent binding of MC to DNA in the above epidermal system. TCPO was effective in increasing the skin tumor initiating ability of MC, DMBA, BP and BP 4,5 epoxide. Mice that were topically treated with tritiated 7,8 BF, about 90% of the label in epidermal homogenates could be extracted into benzene 24 hours after treatment. 94% of the benzene extractable radioactivity was identified as 7,8 BF. The inhibition of skin tumor initiation by 7,8 BF appears to be partially related to its ability to inhibit the formation of electrophilic intermediate(s).