Regulation of Uridine Diphosphate Glucuronosyltransferase Expression by Phenolic Antioxidants

Khosrow Kashfi, Eun K. Yang, Jayanta Roy Chowdhury, Namita Roy Chowdhury, Andrew J. Dannenberg

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Abstract

Dietary antioxidants protect laboratory animals against the induction of tumors by a variety of chemical carcinogens. Among possible mechanisms, protection against chemical carcinogenesis could be mediated via antioxidant-dependent induction of detoxifying enzymes. Therefore, we investigated the effects of two commonly used food preservatives, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), on the expression of UDP-glucuronosyltransferase isoforms in rat liver. Male Wistar rats were fed a control diet or diets containing BHA (0.75%) or BHT (0.5%) for 2 weeks. BHT and BHA increased UDP-glucuronosyltransferase activities in liver microsomes for p-nitrophenol (236 and 218%, respectively), 3-hydroxybenzo(a)pyrene (246 and 175%, respectively), and androsterone (269 and 152%, respectively). Immunoblots showed changes in the amounts of UDP-glucuronosyltransferase isoforms corresponding to the changes in enzyme activities. Northern blot analysis showed that the concentration of UDP-glucuronosyltransferase mRNA paralleled the concentration of enzyme proteins and their respective levels of enzyme activity. BHT, for example, caused about a 250% increase in mRNA using a probe that recognizes the common 3’-domain of bilirubin/ phenol UDP-glucuronosyltransferase mRNAs. In addition to inducing hepatic enzyme activities, BHT and BHA increased the activity of UDP-glucuronosyltransferase in the small intestine and kidney.

Original languageEnglish (US)
Pages (from-to)5856-5859
Number of pages4
JournalCancer Research
Volume54
Issue number22
Publication statusPublished - Nov 1994

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kashfi, K., Yang, E. K., Chowdhury, J. R., Chowdhury, N. R., & Dannenberg, A. J. (1994). Regulation of Uridine Diphosphate Glucuronosyltransferase Expression by Phenolic Antioxidants. Cancer Research, 54(22), 5856-5859.