Regional cholesterol synthesis in the intestinal mucosa of the geneticallyhypercholesterolaemic RICO rat: kinetic study following whole-body gamma-irradiation

Purpose: To investigate regional cholesterol synthesis and kinetics followi ng whole-body gamma-irradiation in the generically hypercholesterolaemic RI CO rat. Materials and methods: Male RICO rats were fed a semi-purified diet for 1 m onth. At 10 weeks old they were exposed to gamma-irradiation (4 Gy, 1.5 Gy/ min) together with controls. At intervals from 1-8 days after irradiation a n intraperitoneal administration of [1-C-14] acetate was given in order to estimate cholesterogenesis in mucosal cells located at different sites in t he small intestine. The protein and DNA contents of the different enterocyt es isolated along the crypt/villus axis in four equal parts of the intestin e were also determined. Results: A marked decrease of the mean quantities of cholesterol, DNA or pr otein in mucosa was seen 1 and 2 days after irradiation, showing the loss o f 30-40% of the intestinal epithelium, An overshoot of the cell amount was observed after 4 days with a return to basal values by 8 days after irradia tion. The kinetic and topological evolution of cholesterol radioactivity, w hich reflects in situ cholesterol synthesis, showed a typical gradient in c ontrols and at 8 days after irradiation. Cholesterogenesis decreased from t he first to the third quarter of the small intestine (duodenum to proximal ileum), and then increased in the fourth quarter (distal ileum). In all seg ments of the small intestine, cholesterogenesis decreased from crypt cells to villus tip. At days 1 and 2 the gradient of cholesterogenesis on the vil lus was abolished. A slow recovery was seen from day 4 with a strong oversh oot of cholesterol synthesis in crypt cells in every part of the small inte stine. Conclusions: The RICO rat is a useful model for studying the effect of irra diation on regional cholesterogenesis in intestinal mucosa. Cholesterol syn thesis in crypt cells was lowered 1 and 2 days after irradiation, over-expr essed after 4 days and subsequently returned to its normal level.