THE IN-VIVO EFFECT OF THE TUMOR PROMOTER 12-O-TETRADECANOYLPHORBOL-13-ACETATE ON N-METHYL-N-NITROSOUREA-INDUCED APOPTOSIS IN MOUSE HAIR-FOLLICLES

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 ha ir follicle matrix cells. Mouse hair follicles were stimulated to grow hair synchronously by plucking resting hairs and MNU was applied to t he plucked skin as the apoptosis inducer. The effects of TPA on MNU-in duced apoptosis, when given at different intervals before or after MNU treatment, were examined. Changes in the percentage of apoptotic cell s among total hair matrix cells after TPA treatment were measured. A s ignificant suppression in levels of MNU-induced apoptosis was observed in the animals receiving TPA 1 to 6 hr following the induction. Admin istration of TPA before MNU caused a reduction in numbers of apoptotic cells over the control groups, but the differences were not significa nt. Determination of the diurnal variation in apoptotic levels in vehi cle-treated mouse hair follicles revealed a relatively constant baseli ne pattern, suggesting that the above apoptotic responses to MNU and T PA were not affected by the background levels of apoptosis, The findin gs provided in vivo evidence which would support the hypothesis that T PA promotes tumorigenesis by preventing carcinogen-initiated cells fro m undergoing apoptotic death. (C) 1997 Society of Toxicology.