DNA adducts in cervical tissue of smokers and non-smokers

Phillips, David H.; Shé, Meadhbh Ni

doi:10.1016/0165-1161(94)90057-4

Cited by 28 publications

(8 citation statements)

References 24 publications

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“…Similar dose-response findings have been reported for PAH smoking related adducts 22,23,26,27 including benzo[a]pyrene. 32 As the risk for cervical neoplasia increases with longer duration and intensity of smoking, 11 it seems reasonable to hypothesise that alkylation damage may then be a substantial contributory factor in this increased risk.…”

Section: Discussionsupporting

confidence: 73%

“…21 DNA adducts have been detected in human cervical tissues. [22][23][24][25][26][27] In most, but not all, of these studies, adduct levels were higher in smokers with the detected adducts, probably arising from exposure to polycyclic aromatic hydrocarbons present in cigarette smoke. However, other DNA adducts, in particular alkylation-induced lesions, may also be present, but would not have been detected by the procedures used.…”

mentioning

confidence: 99%

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N7‐methyldeoxyguanosine levels in DNA isolated from cervical cytology samples are associated with smoking

Harrison

Khan

Dey

et al. 2006

Intl Journal of Cancer

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Smoking has been associated, in epidemiological studies, with an increased risk of cervical neoplasia. This may be in part due to the presence of tobacco-specific nitrosamines in cervical mucous of smokers, which may result in carcinogenic DNA damage. We have thus examined whether cervical DNA contains alkylation damage arising from exposure to methylating agents (N7-methyldeoxyguanosine, N7-MedG). DNA was extracted from cervical cytology samples and N7-MedG levels were measured using an immunoslotblot assay. Ninety percentage of the DNA samples were alkylated and N7-MedG levels (mean, 95% CI) in ever-smokers (1.27, 0.90-1.81 lmol/mol dG) were significantly higher than those in nonsmokers (0.42, 0.20-0.91 lmol/mol dG: p 5 0.005). N7-MedG adduct levels were significantly correlated with number of cigarettes smoked per day and pack years of cigarette smoking in current smokers. There was no association with N7-MedG levels and cervical intraepithelial neoplasia status, age, parity or contraception use. Our study suggests that cervical DNA contains alkylation damage that can arise from exposure to cigarette smoke. ' 2006 Wiley-Liss, Inc.Key words: alkylation; smoking; cervical cancer; N7-methylguanine Cervical cancer is one of the most common neoplastic diseases affecting women with a combined worldwide incidence of almost half a million new cases annually.1 Laboratory and epidemiological research has provided overwhelming evidence that some subtypes of human papillomavirus (HPV) are a ''necessary but insufficient cause'' for cervical cancer.2-5 Therefore, other risk factors are also needed for the initiation and promotion of cervical carcinogenesis.A number of epidemiological studies suggest that cigarette smoking may be an aetiological risk factor for cervical cancer. 6-10The risk for neoplasia appears to increase with longer duration and intensity of smoking. 11,12 The cervix is known to contain enzymes that can metabolise the carcinogens that are present in cigarette smoke, 13,14 and expression of these enzymes may be modified by HPV infection. 14,15 Cigarette-derived chemicals, nicotine and its major metabolite cotinine, have been found in cervical mucus at levels higher than those present in blood serum, [16][17][18][19] and the tobacco-specific nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) is more prevalent in cervical mucus samples from smokers than those from nonsmokers.20 NNK alkylates DNA forming a range of DNA adducts including N7-methyldeoxyguanosine (N7-MedG), a poorly repaired adduct that can act as a biomarker of exposure to alkylating agents. 21 DNA adducts have been detected in human cervical tissues. [22][23][24][25][26][27] In most, but not all, of these studies, adduct levels were higher in smokers with the detected adducts, probably arising from exposure to polycyclic aromatic hydrocarbons present in cigarette smoke. However, other DNA adducts, in particular alkylation-induced lesions, may also be present, but would not have been detected by the procedures used. Our recent r...

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Section: Discussionsupporting

confidence: 73%

mentioning

confidence: 99%

N7‐methyldeoxyguanosine levels in DNA isolated from cervical cytology samples are associated with smoking

Harrison

Khan

Dey

et al. 2006

Intl Journal of Cancer

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“…Significantly higher levels of DNA adducts, detected by 32P-postlabeling, have been found in the cervical epithelium of smokers than of nonsmokers (34,35), an observation that gives some credence to the epidemiological observations, although it does not prove a causal relationship. In these studies significant differences in adduct levels were observed when butanol extraction was used as the enrichment procedure, but not when nuclease P1 digestion was used (34,35). In another study where nuclease P1 digestion was used to enhance sensitivity, elevated adduct levels were detected only in those smokers who were also users of oral contraceptives (36).…”

Section: Smoking-related Dna Adducts In Human Tissuesmentioning

confidence: 83%

DNA Adducts in Human Tissues: Biomarkers of Exposure to Carcinogens in Tobacco Smoke

Phillips¹

1996

Environmental Health Perspectives

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“…A population-based case-control study in Sweden has showed a synergistic effect between cigarette smoking and both HPV16 positivity and HPV16 DNA load on the development of cervical carcinoma in situ (10). It is generally thought that, in addition to carcinogenic effects of cigarette smoke on cervical tissue, such as genotoxic DNA adducts (11) and the presence of mutagens in cervical mucus (12), the excess risk may be mediated by its effects on immunologic control of HPV infections (13). …”

Section: Introductionmentioning

confidence: 99%

Relationship Between Cigarette Smoking and Human Papilloma Virus Types 16 and 18 DNA Load

Koutsky

Castle

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Although cigarette smoking has been associated with increased human papilloma virus (HPV) detection, its impact on HPV DNA load is unknown. Methods: The study subjects were women who were positive for HPV16 and/or HPV18 at enrollment into the Atypical Squamous Cells of Undetermined Significance-Low-grade Squamous Intraepithelial Lesion Triage Study. Assessments of exposure to smoke and sexual behavior were based on self-report. Viral genome copies per nanogram of cellular DNA were measured by multiplex real-time PCR. Linear or logistic regression models were used to assess the relationship between cigarette smoking and baseline viral load. Results: Of the 1,050 women (752 with HPV16, 258 with HPV18, and 40 with both HPV16 and HPV18), 452 (43.0%) were current smokers and 101 (9.6%) were

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DNA adducts in cervical tissue of smokers and non-smokers

Cited by 28 publications

References 24 publications

N7‐methyldeoxyguanosine levels in DNA isolated from cervical cytology samples are associated with smoking

N7‐methyldeoxyguanosine levels in DNA isolated from cervical cytology samples are associated with smoking

DNA Adducts in Human Tissues: Biomarkers of Exposure to Carcinogens in Tobacco Smoke

Relationship Between Cigarette Smoking and Human Papilloma Virus Types 16 and 18 DNA Load

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