IDENTIFICATION OF TOBACCO-SPECIFIC CARCINOGEN IN THE CERVICAL-MUCUS OF SMOKERS AND NONSMOKERS

Background: In 1996, an estimated 15 700 new cases of cancer of the ut erine cervix and 4900 deaths from this disease were expected to occur in the United States. In a recent international study, human papilloma virus DNA was found in more than 90% of cervical tumor specimens exami ned, irrespective of the nationality of the patients from whom the sam ples mere obtained. Although infection with human papillomavirus is th e major known risk factor for the development of cervical cancer, it a lone is not sufficient. Other etiologic factors that have been associa ted with this disease include deficiencies in micronutrients, lower so cioeconomic status, oral contraceptive use, and cigarette smoking, Sev eral compounds from cigarette smoke (nicotine and its major metabolite , cotinine) have been identified in cervical mucus, and the occurrence of smoking-related DNA damage in the cervical epithelium has been doc umented. Purpose: This investigation was conducted to determine for th e first time whether carcinogenic tobacco-specific N-nitrosamines are present in the cervical mucus of cigarette smokers and of nonsmokers ( most likely as a result of environmental exposure). Methods: Cervical mucus specimens from 15 smokers and 10 nonsmokers were subjected to su percritical fluid extraction with the use of carbon dioxide that conta ined 10% methanol, and the resultant extracts were analyzed for tobacc o-specific nitrosamines by use of a very sensitive method that involve d gas chromatography and mass spectroscopy analyses. Results: In a tot al of 16 samples obtained from 15 women who were current smokers (two samples from the same woman), we detected the tobaccospecific nitrosam ine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at concentrat ions that ranged from 11.9 to 115.0 ng/g of mucus. Only one of a total of 10 cervical mucus specimens obtained from 10 women who claimed to be nonsmokers did not contain detectable NNK, and NNK concentrations r anged from 4.1 to 30.8 ng/g of mucus in the specimens; from the remain ing nine women. The concentrations of NNK in specimens from cigarette. smokers mere significantly higher than those from nonsmokers (mean +/ - standard deviation: 46.9 +/- 32.5 ng/g of mucus versus 13.0 +/- 9.3 ng/g of mucus; two-railed Student's t test, P = .004), Conclusion: The cervical mucus of cigarette smokers contains measurable amounts of th e potent carcinogen NNK. This compound represents the first tobacco-sp ecific carcinogen identified in this physiologic fluid of women who sm oke cigarettes. The presence of NNK in the cervical mucus of nonsmoker s is likely due to environmental exposure or to the fact that some of the subjects in this study may not have revealed that they occasionall y smoked cigarettes. Implications: The presence of NNK in human cervic al mucus further strengthens the association between cervical cancer a nd tobacco smoking.