Tobacco smoke as a mouse lung carcinogen.
Male and female strain A/J mice were exposed to environmental tobacco smoke that was generated by burning Kentucky 1R4F reference cigarettes. Exposures lasted 6 hours per day, 5 days per week for a total of 5 months, followed by a 4-month recovery period in air. Chamber concentrations of total suspended particulate matter (TSP) ranged from 50 to 90 mg/m3. Under these conditions, the average lung tumor multiplicity was 1.2 to 1.4 tumors per lung, significantly higher (p < 0.05) than in concomitant controls. ETS exposure led to a comparatively modest increase in cell proliferation in the alveolar zone during the first 2 weeks and in the terminal airways during the first 6 weeks. In the nasal passages cell proliferation was increased throughout, but reverted down to normal when the animals were placed in air. Smoke exposure increased immunostaining for cytochrome P4501A1 in airways and parenchyma. Exposure to the smoke gas phase only produced a similar increase in lung tumor multiplicity as did exposure to full smoke, but failed to induce P4501A1. This suggested that gas-phase constituents play an important role in tobacco smoke carcinogenesis. The strain A/J lung tumor model is thus suitable to study questions associated with tobacco smoke toxicity and carcinogenicity.
Witschi
H
H
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, USA. hrwitschi@ucdavis.edu
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D005260:Female; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D014028:Tobacco Smoke Pollution; D019363:Cytochrome P-450 CYP1A1