Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo-2'-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations

Suryanarayana V. Vulimiri, Xifeng Wu, Wanda Baer-Dubowska, Mariza De Andrade, Michelle Detry, Margaret R. Spitz, John DiGiovanni

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The purpose of this study was to examine the level of smoking-related aromatic DNA adducts and oxidative DNA damage in current smokers from a lung cancer case-control study in African Americans and Mexican Americans. In addition, mutagen sensitivity (bleomycin-induced chromatid breaks), a marker of genetic susceptibility, was assessed in these patients and correlated with the level of DNA damage. Lymphocyte DNA from cases and age-, sex-, and ethnicity-matched controls was analyzed for aromatic DNA adducts (43 cases and 47 controls) and the level of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo- dG) was determined in 46 cases and 48 controls using 32P-postlabeling. Overall, lung cancer cases had significantly (P<0.05) higher levels of aromatic DNA adducts and 8-oxo-dG (mean ± SEM; 6.03 ± 1.16/108 nucleotides and 5.82 ± 0.77/105 nucleotides, respectively) compared to the controls (2.80 ± 0.36/108 nucleotides and 3.65 ± 0.56/105 nucleotides, respectively). The case-control differences for these two biomarkers were especially evident in current smokers. Both male and female lung cancer cases had higher levels of aromatic DNA adducts compared to the corresponding controls but only in men was the difference statistically significant (P=0.002). Cases who started smoking at earliest age had highest levels of aromatic DNA adducts and 8-oxo-dG. The level of aromatic DNA adducts in lung cancer cases, but not controls, was positively correlated with bleomycin- induced chromatid breaks (P=0.011). In contrast, the level of 8-oxo-dG was not correlated with mutagen sensitivity in either cases or controls or with the level of aromatic DNA adducts. The data suggest that levels of both aromatic DNA adducts and 8-oxo-dG may be useful in predicting risk of lung cancer in these minority populations. The correlation between aromatic DNA adducts and mutagen sensitivity in lung cancer cases and the trend for higher levels of DNA damage in cancer cases who started smoking earliest are particularly interesting and merit further study. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)34-46
Number of pages13
JournalMolecular Carcinogenesis
Volume27
Issue number1
DOIs
StatePublished - Feb 23 2000

Keywords

  • 8-oxo-dG
  • Aromatic DNA adducts
  • DNA damage
  • Oxidative stress
  • Smoking

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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