Stimulation of hydroperoxide generation in mouse skins treated with tumor-promoting or carcinogenic agents in vivo and in vitro

Abstract

The levels of hydroperoxides in mouse skin (epidermis + dermis) homogenates incubated in the presence and absence of enzymic and non-enzymic generators of reactive oxygen species are rapidly increased by 12-O-tetradecanoylphorbol-13-acetate (TPA). Moreover, the homogenates prepared from skins treated repeatedly with TPA or 7,12-dimethylbenz[a]anthracene (DMBA) in vivo contain substantially more hydroperoxides, and accumulate more hydroperoxides in the presence of NaN 3 and NADPH, than their counterparts prepared from control skins receiving acetone only. Various agents increase the levels of hydroperoxides in skin homogenates in relation with their tumor-promoting or carcinogen activities, suggesting that an increased level of peroxidation may be involved in the multistage process of skin carcinogenesis.