Effect of temperature on benzo[a]pyrene-induced hyperplastic and neoplastic skin lesions in mice

The time required for tumor development and death in inbred C3H/HeJ mice treated with 1.0 or 0.1 mg benzo(a)pyrene (BP) twice weekly was shortest in mice kept in a cool environment (CE), intermediate in mice kept in a normal temperature environment (NE), and longest in mice kept in a warm environment (WE). Incidence of tumors (predominantly squamous carcinomas) and mortality was 100% by 36 weeks in all environments in the high-dose group. In the low-dose group, by 36 weeks tumor incidence was least in the WE compared with that in the NE and CE. Squamous carcinomas predominated in the NE and CE, but the incidence of fibromas and epithelial hyperplasias exceeded that of squamous carcinomas in the WE. Cutaneous epithelial hyperplasia, considered a preneoplastic change, was evaluated by light and electron microscopy at weekly intervals for 70 days. Increased epidermal thickness was induced by the toluene (T) vehicle alone, was significantly enhanced by BP treatment, and was more severe in mice in the CE and NE than in the WE. Although epithelial hyperplasia induced by BP was interpreted as a preneoplastic lesion, no ultrastructural differences were detected between T- and BP-treated mice in any environment. Results indicated that WE diminished the preneoplastic proliferative response of skin to BP and subsequently delayed the onset of squamous carcinomas induced by high doses of BP and reduced the incidence of squamous carcinomas at low doses of BP.