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

• Published in: Journal of toxicology and environmental health Vol. 23; no. 1; p. 15
• Main Authors: Walaszek, Z, Hanausek-Walaszek, M, Webb, T E
• Format: Journal Article
• Language: English
• Published: United States 1988
• Subjects: Administration, Oral; Animals; Antigens, Neoplasm - biosynthesis; Calcium - administration & dosage; Carcinogens - antagonists & inhibitors; Delayed-Action Preparations; Female; Glucaric Acid - administration & dosage; Glucaric Acid - analogs & derivatives; Glucuronidase - antagonists & inhibitors; Potassium - administration & dosage; Rats; Sugar Acids - administration & dosage
• ISSN: 0098-4108
• DOI: 10.1080/15287398809531093

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 beta-glucuronidase. The sustained-release forms are particularly effective, 1.5 mmol/kg of GL maintaining serum beta-glucuronidase activity at or below 50% for only 1 h, while an equivalent amount of calcium glucarate (CGT) maintained this level of inhibition for over 5 h. CGT 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.