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 β-glucuronidase inhibitor

Zbigniew Walaszek, Malgorzata Hanausek-walaszek, Thomas E. Webb

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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 β-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 β-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 β-glucuronidase increases the proportion of DMBA which is sequestered and excreted as the glucuronide and therefore unavailable for activation to the proximal carcinogen.

Original languageEnglish (US)
Pages (from-to)767-772
Number of pages6
JournalCarcinogenesis
Volume5
Issue number6
DOIs
StatePublished - Jun 1984
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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