EFFECT OF METHYLENE-CHLORIDE INHALATION ON REPLICATIVE DNA-SYNTHESIS IN THE LUNGS OF FEMALE B6C3F(1) MICE

In the National Toxicology Program a-year inhalation study of dichloro methane (DCM), there was a significant increase in pulmonary neoplasms in female B6C3F(1) mice exposed to 2000 ppm (overall rates of 30/48 v ersus 5/50 in control). Replicative DNA synthesis was examined to eval uate the potential role of treatment-induced lung cell proliferation o n pulmonary carcinogenicity. Tritiated thymidine incorporation was ass essed in methacrylate plastic sections after 1, 2, 3, or 4 weeks of in halation exposure to 2000 ppm or 8000 ppm DCM. Similar measurements of labeling indexes were made after 13 and 26 weeks of exposure to 2000 ppm DCM using bromodeoxyuridine as the labeling agent. In all cases th e labeling agent was delivered over a 6-day period using osmotic minip umps. The labeling index (LI) of bronchiolar epithelium (two branches proximal to the terminal bronchiole) of mice exposed to 2000 ppm DCM f or 2-26 weeks decreased to 40-60% of the control. Terminal bronchioles showed a similar decrease in LI. Mice exposed to 8000 ppm DCM had a l ess dramatic decrease in LI. No pathological change was found in the e xposed lungs. It is concluded that inhalation exposure to DCM for up t o 26 weeks reduces cell turnover of bronchiolar cells in female B6C3F( 1) mice.