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

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 NaN3 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.