The effect of bile acids and piroxicam on MHC antigen expression in rat colonocytes during colon cancer development.

The effect of bile acids and piroxicam on the expression of major histocompatibility complex (MHC) antigens in colonocytes was evaluated in rats treated with the colonic carcinogen azoxymethane (AOM). Male Fischer-344 rats were fed a basal diet (AIN-76) supplemented with 0.4% cholic acid, 0.4% ursodeoxycholic acid, 0.2% ursodeoxycholic acid plus 0.2% cholic acid, or 75 p.p.m. piroxicam. Rats were injected subcutaneously once a week for 2 weeks with AOM (15 mg/kg body weight/week) or vehicle, after being fed their respective diets for two weeks. The rats were killed at 16 weeks, while parallel identical groups of rats were killed at 28 weeks, and colon tumours were counted. None of the rats treated with AOM-vehicle developed tumours at 28 weeks, while in the AOM-treated rats the frequency of colonic tumours was as follows: AOM alone 50%, cholic acid 74%, ursodeoxycholic acid 17%, piroxicam 28%, ursodeoxycholic plus cholic acid 46%. The expression of RT1A, RT1B and RT1D was determined in isolated colonocytes by immune fluocytometry. Normal rat colonocytes express all three MHC antigens strongly. Neither the bile acids nor piroxicam affected MHC antigen expression in AOM-vehicle-treated rats. AOM did not effect MHC antigen expression compared to normal controls. Cholic acid had no significant effect on the expression of MHC antigens in AOM-treated rats. Ursodeoxycholic acid alone or in combination with cholic acid increased the expression of RT1A compared to normal controls, of RT1B compared to AOM-treated rats, and of RT1D compared to controls or AOM-treated rats. Piroxicam increased the expression of all three antigens compared to either control or AOM-treated rats. These findings indicate that (1) ursodeoxycholic acid and piroxicam up-regulate colonic MHC antigen expression in the AOM model of colonic carcinogenesis; (2) the colon of rats exposed to AOM responds differently than the normal colon with respect to MHC regulation; and (3) the protective effect of ursodeoxycholic acid and piroxicam on colon tumour formation seems to be paralleled by an increase in MHC antigen expression.