FAILURE OF CIGARETTE-SMOKE TO INDUCE OR PROMOTE LUNG-CANCER IN THE A J MOUSE/

A 6-month bioassay in A/J mice was conducted to test the hypothesis th at chronically inhaled mainstream cigarette smoke would either induce lung cancer or promote lung carcinogenicity induced by the tobacco-spe cific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK ). Groups of 20 female A/J mice were exposed to filtered air (FA) or c igarette smoke (CS), injected with NNK, or exposed to both CS and NNK. At 7 weeks of age, mice were injected once with NNK; 3 days later, th ey were exposed to CS for 6 h/day, 5 days/week, for 26 weeks at a mean 248 mg total particulate matter/m(3) concentration. Animals were sacr ificed 5 weeks after exposures ended for gross and histological evalua tion of lung lesions. No significant differences in survival between e xposure groups was observed. A biologically significant level of CS-ex posure was achieved as indicated by CS-induced body weight reductions, lung weight increases, and carboxyhemoglobin levels in blood of about 17%. Crude tumor incidences, as determined from gross observation of lung nodules, were similar between the CS-exposed and FA groups, surd the NNK and CS + NNK groups. Incidences in either of these latter grou ps were greater than either the CS or FA groups. Furthermore, tumor mu ltiplicity in tumor-bearing animals was not significantly different am ong any of the three groups (FA., NNK, CS + NNK) in which tumors were observed. Thus, CS exposure neither induced lung tumors nor promoted N NK-induced tumors. Because the Cs exposure concentration was probably near the maximally tolerable level, longer exposures should be evaluat ed to potentially establish a CS-induced model of lung carcinogenesis in the A/J mouse.