Epithelial cells of different organs exhibit distinct patterns of p53-dependent and p53-independent apoptosis following DNA insult

The present study shows that DNA damage induces different patterns of p53-d ependent and p53-independent apoptosis in epithelial cells of various organ s of adult mice. Genotoxic stress induced a biphasic apoptotic response in the small intestine and tongue. While the first immediate apoptotic wave wa s p53-dependent, the second was slower in rate and was p53-independent. Und er the same experimental conditions a single rapid, but a more extended, p5 3-independent response was evident in the skin of the tail. Indeed, exposur e of p53+/+ mice to 400 R induced in epithelium of the small intestine and tongue an immediate rapid response that was followed by a second delayed p5 3-independent apoptotic wave. p53-/- mice exhibited in these organs the sec ond wave only. However, epithelium of the tail derived from the same mice s howed a single rapid apoptotic response that lasted much longer than the p5 3-dependent response and was similar in the p53-/- and the p53+/+ mice. Var iations in apoptotic patterns observed in epithelial cells derived of the d ifferent tissues may point to differences in the physiological pathways exp ressed. (C) 1999 Academic Press.