Defective acute apoptotic response to genotoxic carcinogen in small intestine of APC(Min/+) mice is restored by sulindac.
The effect of APC loss on azoxymethane (AOM)-induced apoptosis and cell proliferation, as well as their regulation by sulindac was examined in colon and small intestine in APC(Min/+) mice. APC(Min/+) mice showed increased epithelial proliferation in all regions, with significant impairment of apoptosis in small intestine, but not in colon. Sulindac administration restored defective apoptosis to normal. As the apoptotic defect occurred at the major site of intestinal tumor formation in APC(Min/+) mice and as it was restored to normal by a proven chemopreventive agent, this defect in apoptosis might be a key biological consequence of APC dysfunction contributing to tumor formation.
Hu
Ying
Y
Department of Medicine, Flinders University of South Australia, Adelaide, Australia. ying.hu@flinders.edu.au
Le Leu
Richard K
RK
Young
Graeme P
GP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001397:Azoxymethane / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D017491:Genes, APC; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D013467:Sulindac / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002273:Carcinogens; D013467:Sulindac; D001397:Azoxymethane