The effects of two isomeric benzoflavones on aryl hydrocarbon hydroxylase and the toxicity and carcinogenicity of polycyclic hydrocarbons.

At concentrations 10 to 20 times greater than that of the hydrocarbons, 7,8-benzoflavone (7,8-BF) inhibited almost completely the metabolism of benzo(a)pyrene and 7,12dimethylbenz(a)anthracene (DMBA) to water-soluble deriv atives in hamster embryo cell cultures. The isomer 5,6-benzofiavone (5,6-BF) inhibited metabolism to a much lesser extent. 5,6-BF induced some aryl hydrocarbon hydroxylase (AHH) activity in hamster embryo cells, while 7,8-BF inhibited normal enzyme activity as well as induction of AHH by benz(a)anthracene. 7,8-BF protected hamster embryo cells against cytotoxicity induced by DMBA, benzo(a)pyrene, and 3-methylcholanthrene; 5,6-BF gave slight protection at high concentrations. 7,8-BF was one-tenth as effective as 5,6-BF in protecting rats against DMBA-induced adrenal necrosis; 7,8-BF was also less effective as an inducer of hepatic AHH activity in the rats. A/HeJ mice fed a diet containing 5,6-BF or 7,8-BF showed induced levels of AHH in the liver, lungs, and small intestine. Both flavones inhibited the induction of pulmonary adenomas by DMBA administered p.o. to the mice.