Abstract
OBJECTIVE--To determine whether tobacco smoking causes increased DNA modification (adducts) in human cervical epithelium. DESIGN--Comparison of DNA adducts measured by the technique of postlabelling with phosphorus-32 in normal ectocervical epithelium of smokers and non-smokers. A questionnaire on smoking habit and a urinary cotinine assay were used to identify smokers and non-smokers. SETTING--Cytology unit in large teaching hospital. SUBJECTS--39 women (11 current smokers, seven former smokers, and 21 who had never smoked) undergoing gynaecological treatment (colposcopy or hysterectomy). Nineteen members of staff who did not smoke as controls. INTERVENTIONS--Biopsy of normal ectocervical epithelium. Urine sample. MAIN OUTCOME MEASURES--Measurement of DNA adducts in cervical epithelial tissue of smokers and non-smokers. Smoking habit derived from results of questionnaire and urinary cotinine:creatinine ratio. Proportion of adducts in women with abnormal and normal results of cervical smear test. RESULTS--DNA samples from smokers (identified from questionnaire) had significantly higher median proportions of DNA adducts that non-smokers (4.62 (95% confidence interval 4.04 to 7.74) v 3.47 (2.84 to 4.78) adducts/10(8) nucleotides; p = 0.048). Exclusion of women whose urinary cotinine:creatinine ratio did not confirm their self reported smoking habit (smoker or non-smoker) increased this difference (4.7 (3.85 to 8.08) v 3.52 (2.32 to 4.95) adducts/10(8) nucleotides; p = 0.03). Women who had abnormal results of cervical smear tests had significantly higher proportions of adducts than those with normal results (4.7 (3.90 to 8.13) v 3.47 (3.06 to 5.36) adducts/10(8) nucleotides; p = 0.03). CONCLUSIONS--Tobacco smoking by women leads to increased modification of DNA in cervical epithelium, suggesting biochemical evidence consistent with smoking as a cause of cervical cancer.
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- Benowitz N. L., Kuyt F., Jacob P., 3rd, Jones R. T., Osman A. L. Cotinine disposition and effects. Clin Pharmacol Ther. 1983 Nov;34(5):604–611. doi: 10.1038/clpt.1983.222. [DOI] [PubMed] [Google Scholar]
- Brisson J., Roy M., Fortier M., Bouchard C., Meisels A. Condyloma and intraepithelial neoplasia of the uterine cervix: a case-control study. Am J Epidemiol. 1988 Aug;128(2):337–342. doi: 10.1093/oxfordjournals.aje.a114973. [DOI] [PubMed] [Google Scholar]
- Cuzick J., Routledge M. N., Jenkins D., Garner R. C. DNA adducts in different tissues of smokers and non-smokers. Int J Cancer. 1990 Apr 15;45(4):673–678. doi: 10.1002/ijc.2910450417. [DOI] [PubMed] [Google Scholar]
- Dunn B. P., Vedal S., San R. H., Kwan W. F., Nelems B., Enarson D. A., Stich H. F. DNA adducts in bronchial biopsies. Int J Cancer. 1991 Jun 19;48(4):485–492. doi: 10.1002/ijc.2910480403. [DOI] [PubMed] [Google Scholar]
- Feyerabend C., Russell M. A. Rapid gas-liquid chromatographic determination of cotinine in biological fluids. Analyst. 1980 Oct;105(1255):998–1001. doi: 10.1039/an9800500998. [DOI] [PubMed] [Google Scholar]
- Gupta R. C. Enhanced sensitivity of 32P-postlabeling analysis of aromatic carcinogen:DNA adducts. Cancer Res. 1985 Nov;45(11 Pt 2):5656–5662. [PubMed] [Google Scholar]
- Gupta R. C., Reddy M. V., Randerath K. 32P-postlabeling analysis of non-radioactive aromatic carcinogen--DNA adducts. Carcinogenesis. 1982;3(9):1081–1092. doi: 10.1093/carcin/3.9.1081. [DOI] [PubMed] [Google Scholar]
- McCann M. F., Irwin D. E., Walton L. A., Hulka B. S., Morton J. L., Axelrad C. M. Nicotine and cotinine in the cervical mucus of smokers, passive smokers, and nonsmokers. Cancer Epidemiol Biomarkers Prev. 1992 Jan-Feb;1(2):125–129. [PubMed] [Google Scholar]
- Miller E. C., Miller J. A. Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules. Cancer. 1981 May 15;47(10):2327–2345. doi: 10.1002/1097-0142(19810515)47:10<2327::aid-cncr2820471003>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- Phillips D. H., Hewer A., Malcolm A. D., Ward P., Coleman D. V. Smoking and DNA damage in cervical cells. Lancet. 1990 Feb 17;335(8686):417–417. doi: 10.1016/0140-6736(90)90257-6. [DOI] [PubMed] [Google Scholar]
- Phillips D. H., Hewer A., Martin C. N., Garner R. C., King M. M. Correlation of DNA adduct levels in human lung with cigarette smoking. Nature. 1988 Dec 22;336(6201):790–792. doi: 10.1038/336790a0. [DOI] [PubMed] [Google Scholar]
- Phillips D. H., Schoket B., Hewer A., Bailey E., Kostic S., Vincze I. Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells. Int J Cancer. 1990 Oct 15;46(4):569–575. doi: 10.1002/ijc.2910460403. [DOI] [PubMed] [Google Scholar]
- Randerath E., Miller R. H., Mittal D., Avitts T. A., Dunsford H. A., Randerath K. Covalent DNA damage in tissues of cigarette smokers as determined by 32P-postlabeling assay. J Natl Cancer Inst. 1989 Mar 1;81(5):341–347. doi: 10.1093/jnci/81.5.341. [DOI] [PubMed] [Google Scholar]
- Reddy M. V., Randerath K. Nuclease P1-mediated enhancement of sensitivity of 32P-postlabeling test for structurally diverse DNA adducts. Carcinogenesis. 1986 Sep;7(9):1543–1551. doi: 10.1093/carcin/7.9.1543. [DOI] [PubMed] [Google Scholar]
- Sasco A. J. World burden of tobacco-related cancer. Lancet. 1991 Jul 13;338(8759):123–124. doi: 10.1016/0140-6736(91)90119-a. [DOI] [PubMed] [Google Scholar]
- Sasson I. M., Haley N. J., Hoffmann D., Wynder E. L., Hellberg D., Nilsson S. Cigarette smoking and neoplasia of the uterine cervix: smoke constituents in cervical mucus. N Engl J Med. 1985 Jan 31;312(5):315–316. doi: 10.1056/nejm198501313120516. [DOI] [PubMed] [Google Scholar]
- Schoket B., Horkay I., Kósa A., Páldeák L., Hewer A., Grover P. L., Phillips D. H. Formation of DNA adducts in the skin of psoriasis patients, in human skin in organ culture, and in mouse skin and lung following topical application of coal-tar and juniper tar. J Invest Dermatol. 1990 Feb;94(2):241–246. doi: 10.1111/1523-1747.ep12874576. [DOI] [PubMed] [Google Scholar]
- The disalienation of the NHS. Br Med J. 1978 Jul 1;2(6129):1–2. [PMC free article] [PubMed] [Google Scholar]
- Wilcox R. G., Hughes J., Roland J. Verification of smoking history in patients after infarction using urinary nicotine and cotinine measurements. Br Med J. 1979 Oct 27;2(6197):1026–1028. doi: 10.1136/bmj.2.6197.1026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winkelstein W., Jr Smoking and cervical cancer--current status: a review. Am J Epidemiol. 1990 Jun;131(6):945–960. doi: 10.1093/oxfordjournals.aje.a115614. [DOI] [PubMed] [Google Scholar]