title: Whole body exposure of mice to secondhand smoke induces dose-dependent and persistent promutagenic DNA adducts in the lung.
abstract: Secondhand smoke (SHS) exposure is a known risk factor for lung cancer in lifelong nonsmokers. However, the underlying mechanism of action of SHS in lung carcinogenesis remains elusive. We have investigated, using the (32)P-postlabeling assay, the genotoxic potential of SHS in vivo by determining the formation and kinetics of repair of DNA adducts in the lungs of mice exposed whole body to SHS for 2 or 4 months (5h/day, 5 days/week), and an ensuing one-month recovery period. We demonstrate that exposure of mice to SHS elicits a significant genotoxic response as reflected by the elevation of DNA adduct levels in the lungs of SHS-exposed animals. The increases in DNA adduct levels in the lungs of SHS-exposed mice are dose-dependent as they are related to the intensity and duration of SHS exposure. After one month of recovery in clean air, the levels of lung DNA adducts in the mice exposed for 4 months remain significantly higher than those in the mice exposed for 2 months (P<0.0005), levels in both groups being significantly elevated relative to controls (P<0.00001). Our experimental findings accord with the epidemiological data showing that exposure to smoke-derived carcinogens is a risk factor for lung cancer; not only does the magnitude of risk depend upon carcinogen dose, but it also becomes more irreversible with prolonged exposure. The confirmation of epidemiologic data by our experimental findings is of significance because it strengthens the case for the etiologic involvement of SHS in nonsmokers' lung cancer. Identifying the etiologic factors involved in the pathogenesis of lung cancer can help define future strategies for prevention, early detection, and treatment of this highly lethal malignancy.
authors.affiliation: Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Sang-In
authors.initials: SI
authors.lastname: Kim
authors.forename: Volker M
authors.initials: VM
authors.lastname: Arlt
authors.forename: Jae-In
authors.initials: JI
authors.lastname: Yoon
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Cole
authors.forename: Gerd P
authors.initials: GP
authors.lastname: Pfeifer
authors.forename: David H
authors.initials: DH
authors.lastname: Phillips
authors.forename: Ahmad
authors.initials: A
authors.lastname: Besaratinia
mesh_terms: D000818:Animals; D018736:DNA Adducts / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000633:toxicity*; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D018736:DNA Adducts; D009153:Mutagens; D014028:Tobacco Smoke Pollution