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

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Abstract
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 β‐glucuronidase. The sustained‐release forms are particularly effective, 7.5 mmol/kg of GL maintaining serum β‐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 to DNA and the subsequent induction of tumors in target organs.