title: Immunoperoxidase detection of 4-aminobiphenyl- and polycyclic aromatic hydrocarbons-DNA adducts in induced sputum of smokers and non-smokers.
abstract: Tobacco smoke constituents, 4-aminobiphenyl (4-ABP) and polycyclic aromatic hydrocarbons (PAH) possess carcinogenic properties as their reactive metabolites form DNA adducts. We studied the formation of 4-ABP- and PAH-DNA adducts in induced sputum, a non-invasively obtainable matrix from the lower respiratory tract, of smokers (n=20) and non-smokers (n=24) utilizing a semi-quantitative immunohistochemical peroxidase assay. Smokers had significantly higher levels of 4-ABP-DNA adducts as compared to non-smokers (0. 08+/-0.02 versus 0.04+/-0.01, P=0.001, density of immunohistochemical staining), and the levels of adducts were related to current smoking indices (cigarettes/day: r=0.3, P=0.04 and tar/day: r=0.4, P=0.02). Likewise, smokers had elevated levels of PAH-DNA adducts as compared to non-smokers, however, the differences was not statistically significant (0.13+/-0.02 versus 0. 08+/-0.02, P=0.07). The levels of PAH-DNA adducts were only significantly related to the amount of tar consumed per day (r=0.4, P=0.04) but not to the number of cigarettes smoked per day. Neither the levels of 4-ABP-DNA adducts nor those of PAH-DNA adducts were related to smoking history index (pack years). Further, the levels of 4-ABP-DNA adducts were correlated with those of PAH-DNA adducts (r=0.4, P=0.02). We conclude that immunohistochemistry of 4-ABP-DNA adducts in induced sputum is a specific approach to assess current exposure to tobacco smoke in the lower respiratory tract, however, in the case of PAH-DNA adducts, such analysis is less specific as it does not explicitly reflect the magnitude of the exposure.
authors.affiliation: Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Besaratinia
authors.forename: A
authors.initials: A
authors.lastname: Besarati Nia
authors.forename: H W
authors.initials: HW
authors.lastname: Van Straaten
authors.forename: J C
authors.initials: JC
authors.lastname: Kleinjans
authors.forename: F J
authors.initials: FJ
authors.lastname: Van Schooten
mesh_terms: D000328:Adult; D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D001711:Biotransformation; D018736:DNA Adducts / Q000032:analysis*; D004249:DNA Damage; D005260:Female; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000633:toxicity*; D007124:Immunoenzyme Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D012907:Smoking / Q000378:metabolism*; D013183:Sputum / Q000737:chemistry*
chemical_list: D000611:Aminobiphenyl Compounds; D018736:DNA Adducts; D006841:Hydrocarbons, Aromatic; C006757:4-biphenylamine