The Role of p53 in Bleomycin-Induced DNA Damage in the Lung: A Comparative Study with the Small Intestine

摘要: To elucidate the role of p53 and apoptosis in pathogenesis lung injury, we examined histological changes, expressions p21waf1/cip1 (p21), apoptosis, DNA double strand breaks, cell kinetics, synthesis C57/BL6 mice (p53+/+) deficient for (p53−/−) at 2 hours to 7 days after a single intravenous administration bleomycin. We also compared these parameters between cells small intestinal epithelial explore potential differences their response damage. Bleomycin induced p21 expression p53-dependent manner p53+/+ but neither nor p53−/− mice. In both groups mice, focal inflammation followed by fibrosis was observed, there no evidence apoptosis. Cells with breaks those undergoing were unequivocally increased, cycling fraction remained unchanged, suggesting that detected reflected unscheduled repair damaged DNA. prolonged By contrast, intestine, marked cycle arrest extensive evoked crypt changes milder detectable longer time than Among resting enterocytes villi, observed almost equally groups, significantly delayed These observations imply is mediated largely pathway crypts exclusively p53-independent this particularly important despite difference significance plays an villi. Our results suggest respond bleomycin treatment different ways terms induction carries out essential early damage non-apoptotic mechanism which appears be crucial noncycling enterocytes. Importantly, p53-p21 are unlikely bleomycin-induced tissue injury lung.