Lung tumors in A/J mice exposed to environmental tobacco smoke: estimated potency and implied human risk.
Directly inhaled tobacco smoke is a recognized human lung carcinogen, and epidemiological studies suggest relative risks of about 1.2-1.4 for nonsmoking spouses of smokers typically exposed to environmental tobacco smoke (ETS). While many individual ETS components have been shown experimentally to induce lung tumors, ETS itself was only recently shown to induce lung tumors in a series of studies in which strain A/J mice were exposed to well-defined ETS atmospheres. Data from these studies indicate that ETS exposure clearly can increase combined malignant and benign lung tumors in multiple experiments involving male and female A/J mice, and thus provide convincing evidence that ETS is a positive mouse carcinogen. Tumorigenic potencies estimated from these A/J mouse bioassay data predict a corresponding range of increased human risk (0.2-0.5%) that overlaps that implied by case-control studies showing increased lung cancer risks in lifelong nonsmokers married to smokers. In A/J mice exposed to a significantly tumorigenic ETS concentration, lung tumors were found to be significantly smaller than those in corresponding control mice, and mice so exposed for 9 months had significantly fewer tumors/animal than mice exposed for 5 months followed by 4 months in filtered ETS-free air. These findings support hypotheses that ETS does not promote growth of spontaneous neoplastic foci in A/J mice, and that ETS-induced lung-tumor risk in A/J mice occurs predominantly by genotoxic effects that can be suppressed by reduced cell proliferation associated with chronic, high-level ETS exposure. The results obtained add to evidence that A/J mouse lung tumors induced by ETS provide a relevant biological model of ETS-induced human lung tumors.
Bogen
Kenneth T
KT
Health and Ecology Assessment Division L-396, Lawrence Livermore National Laboratory, University of California, 7000 E. Ave., Livermore, CA 94550, USA. bogen@LLNL.gov
Witschi
Hanspeter
H
D000818:Animals; D001835:Body Weight; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012307:Risk Factors; D012727:Sex Characteristics; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects* / Q000706:statistics & numerical data; D014481:United States / Q000453:epidemiology
D014028:Tobacco Smoke Pollution