Repression by sustained-release ß-glucuronidase inhibitors of chemical carcinogen-mediated induction of a marker oncofetal protein in rodents

The degree of induction of an oncofetal protein marker in rodents by selected chemical carcinogens has been correlated with changes in carcinogenicity induced by dietary D-glucaro-1, 4-lactone (GL) based anticarcinogens. These potent anticarcinogens may act to increase the clearance of carcinogens as glucuronides through the inhibition of ß-glucuronidase. The sustained-release forms are particularly effective, 7.5 mmol/kg of GL maintaining serum ß-glucuronidase activity at or below 50% for only 1 h, while an equivalent amount of calcium glucarate (CCT) maintained this level of inhibition for over 5 h. CCT or other sustained-release inhibitors, when fed to rodents during administration of carcinogens that undergo glucuronidation, caused a marked reduction in the induction of the marker protein. For those systems where other markers of carcinogenesis were also assessed, it was determined that the inhibition of marker-protein induction was quantitatively similar to both the inhibition of binding of the carcinogen o DNA and the subsequent induction of tumors in target organs.