Dietary glucarate as anti-promoter of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis

Carcinogenesis. 1986 Sep;7(9):1463-6. doi: 10.1093/carcin/7.9.1463.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Calcium / pharmacology
  • Diet
  • Female
  • Glucaric Acid / analogs & derivatives
  • Glucaric Acid / pharmacology*
  • Glucuronidase / antagonists & inhibitors
  • Gonadal Steroid Hormones / analysis
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / prevention & control*
  • Rats
  • Rats, Inbred Strains
  • Sugar Acids / pharmacology*

Substances

  • Gonadal Steroid Hormones
  • Sugar Acids
  • aceglatone
  • 9,10-Dimethyl-1,2-benzanthracene
  • Glucuronidase
  • Glucaric Acid
  • Calcium