The effects of skin pretreatment of two strains of Swiss mice, NMRI and CF1, with
beta-naphthoflavone on epidermal
tumors induced by 7,12-dimethylbenz[a]
anthracene (DMBA) have been studied. NMRI Swiss strain exhibits a natural high sensitivity to the carcinogenic effect of the
hydrocarbon, and the pretreatment of mice be
beta-naphthoflavone leads to a large decrease of the formation of
tumors. In contrast, CF1 Swiss mice exhibit a very low sensitivity to the carcinogenic effect of DMBA and a dramatic increase of the tumorigenicity occurs when the animals are pretreated by the inducer. Aryl
hydrocarbon hydroxylase activity in skin homogenates of control and differently induced NMRI and CF1 mice has been measured and compared to (a) the kinetics of disappearance of [3H]DMBA from skin in control and
beta-naphthoflavone-treated mice and (b) the kinetics of the covalent binding of the radioactive
hydrocarbon to skin epidermal
DNA (in control an
beta-naphthoflavone-treated mice). The comparison between these three parameters and the tumorigenicity experiments seem to indicate that an optimal rate of DMBA metabolic activation exists which corresponds to a high level of skin
tumors correlated with
DNA binding of the polycyclic
hydrocarbon. These data might explain some conflicting results which have been reported on the effect of inducers of
aryl hydrocarbon hydroxylases on
tumor induction by
polycyclic aromatic hydrocarbons.