Identification of benzo[a]pyrene metabolites in cervical mucus and DNA adducts in cervical tissues in humans by gas chromatography-mass spectrometry

• Published in: Cancer letters Vol. 146; no. 2; pp. 127 - 134
• Main Authors: Melikian, Assieh A, Sun, Peng, Prokopczyk, Bogdan, El-Bayoumy, Karam, Hoffmann, Dietrich, Wang, Xu, Waggoner, Steven
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.11.1999; Elsevier; Elsevier Limited
• Subjects: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - analysis; Adducts; Alcohol; Aromatic hydrocarbons; Benzo(a)pyrene; Benzo(a)pyrene - metabolism; Benzo(a)pyrene-diol epoxide; Biological and medical sciences; Carcinogenesis; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens; Carcinogens - metabolism; Cervical cancer; Cervical mucus; Cervix Mucus - chemistry; Cervix Uteri - chemistry; Chemical agents; Cigarette smoking; Cigarettes; Cytochrome; Deoxyribonucleic acid; DNA; DNA adducts; DNA Adducts - analysis; Epidemiology; Epithelium; Ethanol; Female; Gas chromatography; Gas Chromatography-Mass Spectrometry; Human cervical tissue; Human papillomavirus; Humans; Laboratories; Mass spectroscopy; Medical sciences; Metabolites; Mucus; Nucleotides; Phenols; Polycyclic aromatic hydrocarbons; Pyrene; Smoke; Smoking; Surgery; Tobacco; Tumors; Womens health; Human cervical tissue; Benzo[a]pyrene; Cervical mucus; DNA adducts; Gas chromatography-mass spectrometry; Human; Metabolite; Tobacco smoking; Non smoker; Carcinogen; Gas chromatography; Tissue; Smoker; DNA; Female; Mass spectrometry; Molecular adduct
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(99)00203-7

Epidemiological studies indicate that cigarette smoking increases the risk of cervical cancer. To address questions regarding possible mechanisms of tobacco-related cervical carcinogenesis, in a pilot study, using supercritical fluid extraction and a gas chromatographic-mass spectrometric (GC-MS) technique, we detected and characterized benzo[a]pyrene and its metabolites, namely B[a]P-dihydrodiols, phenols and tetraols in cervical mucus samples from eight smokers and non-smokers. Twenty-eight epithelial and stromal cervical tissue samples from seventeen patients undergoing surgery for non-malignant disease were quantitatively analyzed for BPDE–DNA adducts by a GC-MS technique. BPDE–DNA adducts were found in 25 samples. The mean level of BPDE–DNA adducts in epithelial cervical tissues of smokers was nearly two-fold greater than that in self-reported non-smokers; P=0.02. The mean number of BPDE-adducts (±SD) in epithelial cervical tissues of smokers was 3.5±1.06 adducts/108 nucleotides while that in non-smokers was 1.8±0.96 adducts/108 nucleotides. The mean number of BPDE-DNA adducts in stromal cervical tissues of the same subjects was 1.8±0.96 adducts/108 nucleotides in smokers and that in the stromal tissues of non-smokers was 1.4±1.1 adducts/108. These results suggest that polynuclear aromatic hydrocarbons (PAHs) from tobacco smoke and other environmental sources can be transported to the cervix where they are metabolized in the cervical epithelium to ultimate carcinogenic agents, although transport of ultimate carcinogenic metabolites from other organs to the cervix cannot be ruled out. Exposure of cervical epithelia to PAHs and their carcinogenic metabolites suggests a potential role of such carcinogens in the pathogenesis of cervical cancer in humans.