DNA-ADDUCTS IN CERVICAL TISSUE OF SMOKERS AND NONSMOKERS

Cervical biopsy samples were taken from 40 women, aged between 31 and 72, undergoing hysterectomies. Twenty-two of the women were smokers, f our were ex-smokers and 14 were non-smokers. DNA was isolated and anal ysed using P-32-postlabelling, after butanol extraction or nuclease P1 digestion enhancement of the adducts. Resolution of the adducts was b y thin-layer chromatography on polyethyleneimine (PEI)-cellulose. The pattern of adducts seen was similar to smoking-related adducts detecte d in other tissues and consisted mainly of a diagonal zone of radioact ivity. With the butanol extraction enrichment method, the levels of ad ducts in DNA from the 22 smokers ranged from 1.65 to 6.04 adducts/10(8 ) nucleotides (mean = 3.70, SD = 1.36), in DNA from non-smokers from 1 .16 to 3.98 (mean = 2.04, SD = 0.77) and in samples from ex-smokers fr om 2.57 to 3.35 (mean = 2.86, SD = 0.37). The increase in adduct level s in smokers compared with non-smokers was highly significant (Mann-Wh itney test p = 0.0005, two-tailed). When analysed by the nuclease P1 d igestion enhancement method, total adduct levels in samples from smoke rs (mean = 2.95, SD = 1.77) were not significantly different (p = 0.3, two-tailed) from levels in non-smokers (mean = 2.34, SD = 0.96). Howe ver, the level of a minor discrete adduct spot was significantly lower (p = 0.02, two-tailed) in smokers (mean = 0.19, SD = 0.36) than in no n-smokers (mean = 0.39, SD = 0.41). The results indicate that some of the DNA adducts detected in cervical epithelium correlate with tobacco smoking and support the hypothesis that smoking-related cervical canc er results from exposure to genotoxic components of cigarette smoke th at become activated to DNA-binding products in this tissue.