CHB is present in dietary cruciferous vegetables at levels up to 100 ppm. CHB (200 mg/kg po) is pancreatotoxic to rats and causes a 7-fold elevation in pancreatic GSH, and a 2-fold elevation in hepatic GSH by 24 h. The relationship between the GSH effect and toxicity, if any, in unknown, as is the mechanism of the GSH effect. Dose-response studies have not yet been carried out, and the ultimate toxin (CHB or metabolite) has not been identified. In addition, the cancer chemoprotective effect of dietary crucifers has been postulated to be related to changes in GSH metabolism, but neither the mechanism nor the compound responsible is known. CHB is a possible candidate. Experiments are planned to examine the dose and the relationships between toxicity of CHB and GSH alterations, and to determine whether or not CHB has any pharmacologic or toxicologic effects at doses typical of dietary intake. Effects of pure CHB will be compared to shredded brussels sprout diets containing equal doses of CHB. CHB metabolism, metabolite identification, ultimate toxin identification, and mechanism of GSH alteration will also be determined. Further, we plan to test chemoprotection by CHB- induced hepatic and pancreatic GSH accumulation against hepatotoxicity of acetaminophen, hepatic carcinogenicity of aflatoxin B1, and pancreatic carcinogenicity of azaserine, using short-term histochemical and histologic assays.
