Inhibition of 7,12-dimethylbenzanthracene-induced rat mammary tumorigenesis by 2,5-di-O-acetyl-D-glucaro-1,4:6,3-dilactone, an in vivo beta-glucuronidase inhibitor

Carcinogenesis. 1984 Jun;5(6):767-72. doi: 10.1093/carcin/5.6.767.


2,5-Di-O-acetyl-D-glucaro-1,4:6,3-dilactone ( DAGDL ) is a slow release form of D-glucaro-1,4-lactone (GL), a non-toxic natural inhibitor of beta-glucuronidase. When administered orally to female rats in conjunction with a carcinogenic dose of 7,12-dimethylbenzanthracene (DMBA), this compound caused a 70% reduction in the number of rats with mammary tumors and 72% reduction in the number of mammary tumors per rat. Co-administration also reduces the induction by DMBA of a 60 kd oncofetal protein, previously shown to be associated with carcinogenesis and tumorigenesis. DAGDL administration depressed beta-glucuronidase activity both in the absence and presence of concurrent treatment with DMBA and also markedly reduced binding of DMBA to organ DNA. The anti-carcinogenic effect of DAGDL appears to be independent of route of administration of DMBA. It is proposed that inhibition of beta-glucuronidase increases the proportion of DMBA which is sequestered and excreted as the glucuronide and therefore unavailable for activation to the proximal carcinogen.

Publication types

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

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / metabolism
  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Benz(a)Anthracenes / toxicity*
  • Blood Proteins / analysis
  • Carrier Proteins / metabolism
  • Cell Nucleus / metabolism
  • Cell-Free System
  • Cytosol / metabolism
  • Female
  • Glucaric Acid / analogs & derivatives
  • Glucaric Acid / pharmacology*
  • Glucuronidase / antagonists & inhibitors*
  • Kinetics
  • Liver / metabolism
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / prevention & control*
  • RNA / metabolism
  • Rats
  • Rats, Inbred Strains
  • Sugar Acids / pharmacology*
  • Tissue Distribution


  • 7,12-dimethylbenzanthracene-binding protein, rat
  • Benz(a)Anthracenes
  • Blood Proteins
  • Carrier Proteins
  • Sugar Acids
  • aceglatone
  • 9,10-Dimethyl-1,2-benzanthracene
  • RNA
  • Glucuronidase
  • Glucaric Acid