DNA adducts in cervical tissue of smokers and non-smokers.
Cervical biopsy samples were taken from 40 women, aged between 31 and 72, undergoing hysterectomies. Twenty-two of the women were smokers, four were ex-smokers and 14 were non-smokers. DNA was isolated and analysed using 32P-postlabelling, after butanol extraction or nuclease P1 digestion enhancement of the adducts. Resolution of the adducts was by thin-layer chromatography on polyethyleneimine (PEI)-cellulose. The pattern of adducts seen was similar to smoking-related adducts detected in other tissues and consisted mainly of a diagonal zone of radioactivity. With the butanol extraction enrichment method, the levels of adducts 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 from 2.57 to 3.35 (mean = 2.86, SD = 0.37). The increase in adduct levels in smokers compared with non-smokers was highly significant (Mann-Whitney test p = 0.0005, two-tailed). When analysed by the nuclease P1 digestion enhancement method, total adduct levels in samples from smokers (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). However, 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 non-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 cancer results from exposure to genotoxic components of cigarette smoke that become activated to DNA-binding products in this tissue.
Phillips
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Haddow Laboratories, Institute of Cancer Research, Sutton, UK.
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D000328:Adult; D000367:Age Factors; D000368:Aged; D001345:Autoradiography / Q000379:methods; D001706:Biopsy; D002584:Cervix Uteri / Q000737:chemistry* / Q000473:pathology; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D010761:Phosphorus Radioisotopes; D012907:Smoking
D018736:DNA Adducts; D010761:Phosphorus Radioisotopes