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Differential effect of over-expressing UGT1A1 and CYP1A1 on xenobiotic assault in MCF-7 cells

Hau Y Leung1, Yun Wang, Lai K Leung

  • 1Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.

Toxicology
|November 6, 2007
PubMed

Insights

UDP-glucuronosyltransferase (UGT1A1) expression protects breast cancer cells from xenobiotic damage, unlike cytochrome P450 (CYP1A1). Overexpressing UGT1A1 reduced DNA binding and damage from carcinogens like DMBA.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Gene mutations are critical in carcinogenesis, with some genes interacting with environmental factors to promote cancer.
  • Cytochrome P450 (CYP) 1A1 and UDP-glucuronosyltransferase (UGT1A1) are key drug-metabolizing enzymes implicated in breast cancer risk.
  • Xenobiotics, environmental substances metabolized by CYP1A1 and UGT1A1, can contribute to cancer development.

Purpose of the Study:

  • To investigate the role of overexpressed CYP1A1 and UGT1A1 in breast cancer cells (MCF-7).
  • To evaluate the interaction of these enzymes with estrogen and polycyclic aromatic hydrocarbons (PAHs).
  • To determine the protective effects of UGT1A1 and CYP1A1 against xenobiotic-induced DNA damage.

Main Methods:

  • Overexpression of UGT1A1 and CYP1A1 in MCF-7 breast cancer cells.
  • Treatment with estradiol and 7,12-Dimethylbenz[a]anthracene (DMBA), a known carcinogen.
  • Assessment of cell proliferation, DMBA-DNA binding, and DNA damage using comet assays.

Main Results:

  • UGT1A1 overexpression reduced cell proliferation under estradiol treatment.
  • Overexpression of UGT1A1 decreased DMBA binding to DNA and protected cells from DMBA-induced damage.
  • CYP1A1 overexpression intensified DMBA binding to DNA and increased cellular damage.

Conclusions:

  • UGT1A1 expression confers protection against xenobiotic assault in breast cancer cells.
  • CYP1A1 expression exacerbates damage from xenobiotics like DMBA.
  • Differential roles of phase I (CYP1A1) and phase II (UGT1A1) enzymes in breast cancer chemoprevention warrant further investigation.

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