Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis.
Using as a criterion the inhibition of serum beta-glucuronidase activity, dietary calcium D-glucarate is shown to serve as an efficient slow-release source in vivo of D-glucaro-1,4-lactone, the potent endogenous inhibitor of this enzyme. Using the 7,12-dimethylbenz[a]anthracene model of mammary tumor induction in rats it is shown for the first time that feeding the rats calcium D-glucarate-supplemented diet after treatment with the carcinogen, inhibits tumor development by over 70%. Supportive evidence is presented for the theory that calcium D-glucarate inhibits or delays the promotion phase of mammary carcinogenesis by lowering endogenous levels of estradiol and precursors of 17-ketosteroids. Therefore, dietary glucarate can be used to lower blood and tissue levels of beta-glucuronidase, and in turn of those carcinogens and promoting agents which are excreted, at least in part, as glucuronide conjugates.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004032:Diet; D005260:Female; D005937:Glucaric Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors; D012739:Gonadal Steroid Hormones / Q000032:analysis; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D013400:Sugar Acids / Q000494:pharmacology*
D012739:Gonadal Steroid Hormones; D013400:Sugar Acids; C038936:aceglatone; D015127:9,10-Dimethyl-1,2-benzanthracene; D005966:Glucuronidase; D005937:Glucaric Acid; D002118:Calcium