P53 PROTEIN EXPRESSION AND CONCURRENT APOPTOSIS INDUCED BY GAMMA-IRRADIATION OR N-METHYL-N-NITROSOUREA IN NORMAL AND P53-MUTANT MOUSE HAIR-FOLLICLES

The kinetic changes in levels of p53 protein expression were examined in the hair follicles of CD1 mice, following a single cutaneous exposu re to gamma-ray cobalt 60 (Co-60) Or the DNA-alkylating carcinogen N-m ethyl-N-nitrosourea (MNU). Concurrent changes in apoptosis frequency w ere also assessed in hair follicles of CD1 mice and p53-mutant (pL53-1 ) transgenic mice. The p53 protein expression in both Co-60- and MNU-t reated mice was demonstrated in vivo by immunoperoxidase staining. The Co-60-induced p53 expression was rapid and persisted over the 48 h ex perimental period, whereas the MNU-elicited p53 elevation was slower t o appear and lasted a shorter period of time. Both Co-60- and MNU-trig gered p53 elevations were followed in approximately 4 h by increased a poptosis frequency. Hair follicles of mutant pL53-1 transgenic mice, w ith a loss-of-function phenotype, exhibited greatly reduced apoptotic rates after exposure to MNU. This is the first in vivo study which sho ws an intimate correlation and a possible inductive role of p53 protei n in either physical or chemical carcinogen-induced apoptosis in mouse hair follicles.