The correlations between BRCA1 defect and environmental factors in the risk of breast cancer

Hyo Jin Kang, Young Bin Hong, Yong Weon Yi, Chi Heum Cho, Antai Wang, Insoo Bae

Research output: Contribution to journalLetterpeer-review

11 Scopus citations

Abstract

The risk factors for breast cancer, the most common female malignant cancer, include environmental factors such as radiation, tobacco, a high-fat diet, and xenoestrogens as well as hormones. In addition, BRCA1 and BRCA2 are the most well-known genetic factors that increase risk for breast cancer. Coincidence of those environmental and genetic factors might augment the risk of tumorigenesis of breast. To verify this hypothesis, we briefly evaluated the carcinogenic potency of various environmental factors in the absence or presence of BRCA1 as a genetic factor in a normal mammary epithelial cell line, MCF10A. Many environmental factors tested increased cellular ROS level in the absence of other insult. In addition, TCDD, DMBA, 3MC, and BPA enhanced the BaP-induced ROS production. BRCA1 knockdown (BRCA1-KD) cells by siRNA significantly induced cellular accumulation of ROS compared to control cells. In this setting, the addition of paraquat, TCDD, DMBA, 2OHE2 or 4OHE2 significantly augmented ROS generation in BRCA1-KD MCF10A cells. Measurements of BaP-DNA adduct formation as a marker of DNA damage also revealed that BRCA1 deficiency leads increased DNA damage. In addition, TCDD and DMBA significantly increased BaP-DNA adduct formation in the absence of BRCA1. These results imply that elevated level of ROS is correlated with increase of DNA damage in BRCA1 defective cells. Taken together, our study suggests that several environmental factors might increase the risk of tumorigenesis in BRCA1 defective breast epithelial cells.

Original languageEnglish (US)
Pages (from-to)355-361
Number of pages7
JournalJournal of Toxicological Sciences
Volume38
Issue number3
DOIs
StatePublished - Jun 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Toxicology

Keywords

  • BRCA1
  • Breast cancer
  • Environmental factors
  • Genetic factor
  • Tumorigenesis

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