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

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 H -deoxyguanosine (8-oxo-dG) was determined in 46 cases and 48 controls using 32 P-postlabeling. Overall, lung cancer cases had significantly (P`0.05) higher levels of aromatic DNA adducts and 8-oxo-dG (mean AE SEM; 6.03 AE 1.16/10 8 nucleotides and 5.82 AE 0.77/10 5 nucleotides, respectively) compared to the controls (2.80 AE 0.36/10 8 nucleotides and 3.65 AE 0.56/10 5 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.

DNA adduct burden and tobacco carcinogenesis

“…Among these former smokers early age of smoking initiation was the most important predictor of interindividual variations in lung DNA adduct levels after adjusting for other measures of cigarette consumption (Wiencke et al, 1999). Aromatic-DNA adducts were also found to be increased in smokers who started smoking at an early age in another study (Vulimiri et al, 2000). Time elapsed since quitting smoking would seem a logical inverse predictor of DNA adducts in former smokers but this has not been reported.…”

“…Daily cigarette consumption in current smokers also predicted PAH -DNA adduct levels in cardiac tissue from patients undergoing open heart surgery (van Schooten et al, 1998). Nonetheless some investigations have reported higher levels of aromatic-DNA adducts in former smokers (Vulimiri et al, 2000). Earlier suggestions (Phillips et al, 1988) that DNA adducts may reflect lifetime cumulative tobacco smoke exposure as estimated by the packyear variable do not appear to have been substantiated.…”

“…Another group, using microsatellite markers close to hMLH1, reported a similar increase in PAH -DNA adduct levels in lung tissues of lung cancer patients whose tumors contained LOH at 3p21 (Zienolddiny et al, 2001), although the question of age at smoking initiation was not addressed in the latter study. In a study of lymphocytes from lung cancer patients and controls, the highest aromatic DNA adduct levels were observed among cases who started smoking before 15 years of age (Vulimiri et al, 2000).…”

“…Studies of DNA adducts in lung cancer patients have indicated higher adduct levels in lung tissue of cancer cases (Cheng et al, 2000b(Cheng et al, , 2001) and in their peripheral white blood cells (Vulimiri et al, 2000;Perera et al, 1989) compared with controls. Higher adduct levels were reported in lung tissue from women compared with men (Cheng et al, 2001).…”

Teen smoking, field cancerization, and a "critical period" hypothesis for lung cancer susceptibility.

“…We (26,27) and others (28) have observed associations of tobacco-related DNA damage and mutational changes with self-reported age at smoking initiation in patients with lung cancer. Most significantly, younger ages of smoking initiation were associated with a higher prevalence of chromosomal deletions within the specific genomic region implicated in field cancerization in the lung (i.e., 3p21).…”