Six-Month Exposure of Strain A/J Mice to Cigarette Sidestream Smoke: Cell Kinetics and Lung Tumor Data

Abstract Six-Month Exposure of Strain A/J Mice to Cigarette Sidestream Smoke: Cell Kinetics and Lung Tumor Data. Witschi, H. P., Oreffo, V. I. C., and Pinkerton, K. E. (1995). Fundam. Appl. Toxicol. 26, 32-40. Male strain A/J mice were exposed to sidestream smoke (SS) generated from burning Kentucky 1R4F reference cigarettes. Chamber concentrations were 4 mg/m 3 of total suspended respirable particulate matter (TSP). Animals were exposed 6 hr a day, 5 days a week. One-week cumulative labeling indices were significantly increased in the large intrapulmonary airways during the 1st week and in the respiratory epithelium of the nasal and maxillar turbinates during the first 3 weeks of exposure and then returned to control values. Subsequently, signs of increased cell proliferation were again found in the nasal and maxillar turbinates during the 9th and 16th exposure weeks. The experiment was terminated after 6 months. The number of animals bearing lung tumors was the same in smoke-exposed as in filtered air-exposed animals as was the average number of tumors per lung. Analysis of the DNA of individual tumors obtained from exposed and control mice for K-ras mutations suggested that exon 2 might be a specific target for SS. It was concluded that (1) duration of exposure was too short or (2) concentration or TSP was too low to reveal a possible carcinogenic potential of SS in strain A/J mice or that (3) SS is not carcinogenic in strain A mice.