Repression by sustained-release beta-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 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.
Walaszek
Z
Z
Department of Physiological Chemistry, Ohio State University College of Medicine, Columbus.
Hanausek-Walaszek
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M
Webb
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D000284:Administration, Oral; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D002118:Calcium / Q000008:administration & dosage; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D003692:Delayed-Action Preparations; D005260:Female; D005937:Glucaric Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000008:administration & dosage; D051381:Rats; D013400:Sugar Acids / Q000008:administration & dosage*
D000951:Antigens, Neoplasm; D002273:Carcinogens; D003692:Delayed-Action Preparations; D013400:Sugar Acids; C031192:oncofetal antigens; C038936:aceglatone; C009194:saccharolactone; D005966:Glucuronidase; D005937:Glucaric Acid; D011188:Potassium; D002118:Calcium