Six-month exposure of strain A/J mice to cigarette sidestream smoke: cell kinetics and lung tumor data.
Witschi-H; Oreffo-VIC; Pinkerton-KE
Fundam Appl Toxicol 1995 Jun; 26(1):32-40
The carcinogenic potential of sidestream cigarette smoke (environmental tobacco smoke) (ETS) was studied in mice. Male A/J-mice were exposed to filtered air or ETS generated from burning Kentucky 1R4F reference cigarettes for 6 hours/day, 5 days/week for up to 6 months. The smoke had a total suspended particulate concentration of around 4mg/m3. Selected animals were implanted with bromo-2-deoxyuridine (BrUd) containing osmotic minipumps at the start of weeks 1, 2, 3, 4, 6, 9, or 16. They were killed at the end of these weeks and the epithelial cells of the airways were collected. The extent of cell proliferation was assessed by counting the number of BrUd labeled cells, from which labeling indices (LIs) were computed. The remaining mice were killed at the end of 6 months and necropsied, the necropsies focusing on lung tumorigenesis. The DNA was extracted from selected lung tumors and the spectrum of mutations of exons one and two of the K-ras gene was examined. In the respiratory epithelial lining of the nasal and maxillar turbinates, the LIs were significantly increased during the first 3 weeks of exposure, after which they began to return toward the control values. LIs in the large airways were significantly increased in ETS exposed mice at weeks one and three and in the terminal bronchioles at week three. The incidence of lung tumors in the smoke exposed animals did not differ from that in the controls, being 12% in both groups. Lung tumor multiplicity did not differ significantly between the two groups. All lung tumors from ETS exposed mice had K-ras mutations; only 79% of the control mice had these mutations. Most of the K-ras mutations in the smoke exposed mice were in exon two. These mutations in control mice were approximately equally distributed between exons one and two. The authors conclude that 6 months of exposure to ETS at a concentration of 4mg/m3 has few effects in the lungs of A/J-mice. Possible reasons for the negative findings are that a mouse lung tumor assay does not detect ETS carcinogenicity or ETS is not a lung carcinogen in A/J-mice.
Tobacco-smoke; Environmental-exposure; In-vivo-studies; Laboratory-animals; Inhalation-studies; Lung-cancer; Mutagenesis; Cell-division; Nucleic-acids
Christopher E. Mackay, Departments of Avian Science and Environmental Toxicology, University of California, Davis, California, 95616
Fundamental and Applied Toxicology
University of California - Davis