Carcinogen-Induced DNA Double Strand Break Repair in Sporadic Breast Cancer

Cindy Zhang, Elizabeth Naftalis, David Euhus

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Induction of DNA double strand breaks and alterations in the repair of these breaks is implicated in breast carcinogenesis. Prior studies have demonstrated that peripheral blood mononuclear cells (PBMC) from breast cancer patients exhibit increased numbers of DNA strand breaks after exposure to ionizing radiation, but these studies did not specifically measure DNA double strand breaks and it is not known whether chemical carcinogens produce similar effects. Materials and methods: PBMC from 32 women undergoing breast surgery were genotyped at nine loci of seven DNA repair genes. DNA double strand break repair was measured using the neutral comet assay after exposure to ionizing radiation (0.5 Gy) or bioactivated benzo[a]pyrene (B[a]P, 5 μM. Results: PBMC from breast cancer patients showed higher levels of residual DNA double strand breaks 30 min after exposure to radiation than PBMC from patients with benign breast disease (1.40 times baseline [95% confidence intervals [CI] 1.29-1.51] versus 1.24 times baseline [95% CI 1.15-1.33], respectively, P = 0.04). The response to B[a]P trended in the same direction, but did not reach statistical significance. The MGMT K178R variant genotype was associated with improved DNA double strand break repair in PBMC exposed to B[a]P. Conclusions: Reduced repair of radiation-induced DNA double strand breaks in PBMC is a robust biomarker of breast cancer risk. Reduced DNA repair capacity may have a genetic component even in sporadic breast cancer.

Original languageEnglish (US)
Pages (from-to)120-128
Number of pages9
JournalJournal of Surgical Research
Volume135
Issue number1
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • DNA repair
  • benzo[a]pyrene
  • breast neoplasms
  • comet assay
  • ionizing radiation
  • peripheral blood mononuclear cells
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Surgery

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