Daily variations in the duodenal crypts colchicine induced apoptosis

GONZÁLEZ NV; BADRÁN AF; BARBEITO CG

CHRONOBIOLOGY INTERNATIONAL

Taylor & Francis

Lugar: Londres; Año: 2005 vol. 22 p. 79 - 88

0742-0528

Apoptotic cell death can be induced by several agents, among them colchicine?a microtubule disrupting-drug that affects continuously renewing cell populations, such as the intestinal crypt enterocytes. The objectives of this investigation were (1) to confirm in vivo colchicines-inductive effect and (2) to determine the existence of 24 h variations in the crypt enterocytes apoptotic indices. The study was done on C3H/S male adult mice housed under standardized conditions. Starting at midnight until the end of a circadian period, subgroups of mice were sacrificed after having been injected with colchicine or saline i.p. 4h beforehand. Duodenal samples were processed for hematoxylin-eosin staining and TUNEL technique. In order to score the number of apoptosis, the longitudinal sections of the crypts were divided into three regions comprised, respectively, of tiers 1?4, 5?12, and 13?20, proceeding from the bottom to the top of the crypt. Values of each lot were expressed as mean+SEM. A highly significant statistical difference in apoptotic indices was found for colchicine-treated animals. The 24 h curve for colchicineinduced apoptosis displayed qualitative and quantitative differences compared to other inducer agents. Highest apoptotic indices were found in the deepest crypt regions. Daily variations were observed in all the crypt sectors of the colchicine-treated animals and in tiers 5?12 of the saline controls. The present work demonstrates that the colchicine cytotoxicity is due to its apoptoticinducing effect depends on the dosing time during the 24 h in this mouse strain