The in Vivo Effect of the Tumor Promoter 12-O-Tetradecanoylphorbol-13-acetate on N-Methyl-N-nitrosourea-Induced Apoptosis in Mouse Hair Follicles

Abstract

This study assessed the in vivo relationship between apoptosis induced by the tumor initiator N-methyl-N-nitrosourea (MNU) and action of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse hair follicle matrix cells. Mouse hair follicles were stimulated to grow hair synchronously by plucking resting hairs and MNU was applied to the plucked skin as the apoptosis inducer. The effects of TPA on MNU-induced apoptosis, when given at different intervals before or after MNU treatment, were examined. Changes in the percentage of apoptotic cells among total hair matrix cells after TPA treatment were measured. A significant suppression in levels of MNU-induced apoptosis was observed in the animals receiving TPA 1 to 6 hr following the induction. Administration of TPA before MNU caused a reduction in numbers of apoptotic cells over the control groups, but the differences were not significant. Determination of the diurnal variation in apoptotic levels in vehicle-treated mouse hair follicles revealed a relatively constant baseline pattern, suggesting that the above apoptotic responses to MNU and TPA were not affected by the background levels of apoptosis. The findings provided in vivo evidence which would support the hypothesis that TPA promotes tumorigenesis by preventing carcinogen-initiated cells from undergoing apoptotic death.