PMID: 8603388Apr 1, 1996Paper

Reduced bile acid-induced apoptosis in "normal" colorectal mucosa: a potential biological marker for cancer risk

Cancer Research
H GarewalC Payne

Abstract

Dietary factors, including bile acids, are important in the causation of colorectal cancer (CRC). We have previously shown that in vitro exposure of colorectal mucosal biopsies to low concentrations of bile acids produces apoptosis selectively in goblet cells. Apoptosis is an important mechanism for clearing DNA-damaged cells. Inhibition of apoptosis would result in increasing accumulation of DNA-damaged cells, resulting in increased cancer risk. We compared the percentage of apoptosis induced by bile acids in mucosal biopsies from CRC patients with that of noncancer subjects. Mucosal biopsies from 15 to 20 cm from the anal verge were incubated in 1 mM sodium deoxycholate, and the percentage of goblet cells undergoing apoptosis was quantitated. Seven patients with a history of CRC within the previous 5 years were compared with 18 noncancer subjects [4 neoplasia free and 14 with small (< or = 9 mm) polyps only]. The CRC patients had a significantly lower percentage of apoptosis than noncancer subjects; the mean for CRC was 10.7% (range, 0.9-26%) and for noncancer subjects was 55.9% (range, 20.3-71%; P < or = 0.001). Two other noncancer patients had very high-risk lesions, i.e., large villous adenomas and multiple large polyps du...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