Apoptosis in small intestinal epithelial from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation

Oncogene
A J MerrittJ A Hickman

Abstract

The death of small intestinal epithelial cells has been characterized and quantitated after irradiation of mice rendered homozygously null for the p53 gene. In wild-type animals homozygous for p53 a rapid (4.5 h) elevation of p53 protein was observed in the proliferative compartment of the crypts after 8 Gy of irradiation. Cells underwent cell death by apoptosis in this region. We had reported previously a total repression of apoptosis in small intestinal crypt epithelia 4.5 h after the gamma-irradiation (8 Gy) of p53 homozygously null animals. Thus, while 400 apoptotic cells were observed in 200 half crypts taken from wild-type animals at 4.5 h, this fell to background levels (10-30) in the p53 null animals (Merritt et al., 1994) and did not increase by 12 h. However, we have now found a delayed initiation of a p53-independent apoptosis after 8 Gy of gamma-radiation: at 24 h, approximately 100 apoptotic cells were observed in 200 half crypts. This late wave of apoptosis was not observed after 1 Gy of gamma-radiation. The morphological appearance of this p53-independent apoptosis suggested that death may have arisen as the result of aberrant mitosis. Analysis of the regeneration of crypts 3 days after irradiation of mice with b...Continue Reading

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis