REPLICATIVE DNA-SYNTHESIS IN TISSUES OF THE RAT EXPOSED TO AGED AND DILUTED SIDESTREAM SMOKE

Male Sprague-Dawley rats were exposed to aged and diluted sidestream s moke (ADSS) from Kentucky 1R4F reference cigarettes for 6 h/day, 5' da ys/wk, for a 13-wk period. Exposure concentrations were 0, 0.1, 1, and 10 mg ADSS/m(3). Exposures were conducted in whole-body inhalation ch ambers. Rats were held in nose-only exposure tubes for the 6-h exposur es to minimize pelt deposition and subsequent ingestion of ADSS. Group s of 10 rats from each exposure group were killed after 5, 28, and 90 d of exposure to examine the rates of replicative DNA synthesis; 6 rat s from each exposure group were kept for a 90-day recovery period afte r termination of exposures to examine replicative DNA synthesis rates. Three days prior to each scheduled necropsy, an osmotic pump containi ng 5-bromo-2'-deoxyuridine (BrdU) was implanted subcutaneously. After necropsy, tissues were processed for examination of BrdU-containing ce lls at several sites. Incorporation of BrdU was assessed either by cou nting the number of labeled cells along a length of an epithelial surf ace or by counting the number of labeled cells in an area of tissue. T issues examined were from the nasal cavity, ventral larynx, and trache a, in addition to bronchial, bronchiolar, and alveolar regions of the lung. Endocardium, myocardium, epicardium, and aortic smooth muscle si tes were also examined. Increased replicative DNA synthesis occurred i n some sites of the respiratory tract at the 5-day timepoint at the mi d or high exposure concentrations, although at 28 and 90 days, these e ffects had diminished in intensity or were not present, indicating ada ptation to the ADSS exposure. The only tissues with elevated rates of replicative DNA synthesis at 90 days were the cuboidal and respiratory epithelium at the most rostral portion of the nasal cavity at the hig hest exposure concentration. Increased rates of replicative DNA synthe sis were not noted in heart tissues or lung alveolar epithelium at any concentration at any time point. Examination of rats killed after the end of the 90-day recovery period indicated that the increase in repl icative DNA synthesis was not sustained after termination of exposures . The no observed effect level (NOEL) for increased replicative DNA sy nthesis after subchronic exposure to ADSS in the rat is greater than 1 mg ADSS/m(3).