Detection and measurement of DNA adducts in the cervix of smokers and non-smokers

Ali, Sarina; Astley, Siân; Sheldon, T; Peel, K. R.; Wells, Michael

doi:10.1046/j.1525-1438.1994.04030188.x

Cited by 18 publications

(9 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 86%

“…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: 72%

See 1 more Smart Citation

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

Harrison

Khan

Dey

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 72%

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

Harrison

Khan

Dey

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…An increased risk of cervical cancer associated with tobacco smoking has been established on the basis of a number of epidemiologic studies since the 1980s (4,5). Whether this link is related to genotoxic DNA adducts of smoking in the cervix epithelium (6)(7)(8), its effect on malignant transformation of HPV-infected cells (9), or its influence on HPV infections via localized immunosuppression (10) has been discussed. It has also been debated whether an association of smoking and cervical cancer is merely an artifact of confounding by HPV because of association of smoking with sexual activity and the subsequent risk of acquiring an HPV infection (11,12).…”

Section: Introductionmentioning

confidence: 99%

Synergy between Cigarette Smoking and Human Papillomavirus Type 16 in Cervical Cancer In situ Development

Gunnell

Tran

Torrång

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background: A majority of studies have implicated the involvement of cigarette smoking in cervical cancer development, although its mechanism of action remains unclear. We conducted a large population-based case-control study to address the potential interaction between smoking and human papillomavirus type 16 (HPV-16) in development of cervical cancer in situ (CIS). Methods: Information on risk factors for CIS was collected via interview, and archival cervical smears were tested for HPV-16 DNA presence in cases (n = 375) and controls (n = 363). Adjusted odds ratios (OR) for the effects of smoking, HPV-16 presence/absence, and load at first smear (taken, on average, 9 years before diagnosis) were calculated. Results: The risk for CIS among current smokers who were HPV-16 positive at time of first smear was >14-fold [adjusted OR, 14.4; confidence interval (95% CI), 5.6-36.8] compared

show abstract

“…Smoking may affect a number of pathways leading to cancer; generally, smoking is associated with metaplasia, neoangiogenesis and proliferation in epithelium and with overexpression of p53 and Ki-67 in dysplasias (14,15). In addition, smoking has been associated with the formation of chemically stable DNA adducts in cervical epithelium that may induce genetic instability (14,(16)(17)(18). Last, tobacco byproducts may modulate inflammation and local immunity and may perturb apoptotic pathways (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

“…Dissecting the role that smoking plays at each phase of infection and carcinogenesis could better inform our interventions and prevention strategies. Cross-sectional data from 205 women, ages 16 to 23 years, who tested positive for HPV16 DNA at their first study visit were analyzed to determine whether smoking was associated with detection of HPV16-L1 antibody in serum specimens (anti-HPV16 antibody).…”

Section: Introductionmentioning

confidence: 99%

Smokers at Higher Risk for Undetected Antibody for Oncogenic Human Papillomavirus Type 16 Infection

Wiley

Wiesmeier

Masongsong

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Objective: To determine the association between tobacco smoking and serologic evidence of human papillomavirus type 16 (HPV16) -specific antibodies among HPV16 DNApositive women. Design, Setting, and Participants: Baseline health history, physical examination, and laboratory data for 205 HPV16 DNA -positive women with no prior cytologic evidence of squamous intraepithelial lesions who were enrolled subsequently in a randomized clinical trial. Main Outcome Measure: HPV16-L1 antibody (anti-HPV16 antibody) detected from serum using RIA or ELISA. Results: Eighty-seven percent (179 of 205) of women tested positive for HPV16 DNA using cervicovaginal swabs or lavage specimens, and 26 women showed similar results using swab specimens of external genitalia alone. HPV16-infected women who reported increasingly greater levels of daily cigarette smoking were less likely to test positive for anti-HPV16 antibodies than nonsmoking women (P = 0.02).Smokers were twice as likely as nonsmokers to test negative for anti-HPV16 antibodies, even after controlling for the effects of other covariates in the analyses (adjusted odds ratio, 0.5; 95% confidence limits, 0.2-0.9). Although Papanicolaou test findings and smoking characteristics were poorly correlated (r 2 = 0.01), women who showed atypical cells of unknown significance or squamous intraepithelial lesion were twice as likely to test anti-HPV16 antibody positive as women who showed normal Papanicolaou tests (adjusted odds ratio, 2.0; 95% confidence limits, 1.1-3.7).

show abstract

Detection and measurement of DNA adducts in the cervix of smokers and non-smokers

Cited by 18 publications

References 17 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

Synergy between Cigarette Smoking and Human Papillomavirus Type 16 in Cervical Cancer In situ Development

Smokers at Higher Risk for Undetected Antibody for Oncogenic Human Papillomavirus Type 16 Infection

Contact Info

Product

Resources

About