Pilot studies evaluating the lung tumor yield in cigarette smoke-exposed mice

In spite of the major role played by cigarette smoking in the epidemiology of lung cancer, it is very difficult to reproduce the carcinogenicity of th is complex mixture in animal models. We implemented a series of pilot exper iments in three mouse strains, exposed either to environmental cigarette sm oke (ECS) or mainstream cigarette smoke (MCS) or its condensate (MCSC). The whole-body exposure of Aroclor-treated A/J mice to ECS resulted in a rapid and potent induction of micronuclei in peripheral blood erythrocytes. Afte r 6 months of exposure, 6 h a day, followed by 4 months of recovery in filt ered air, both lung tumor incidence and multiplicity were significantly inc reased as compared to sham-exposed mice (77.8% vs. 22.2%, and 1.11 +/- 0.26 vs. 0.22 +/- 0.15, means +/- SE). Multiple i.p. injections of butylated hy droxytoluene did not significantly enhance the tumor yield. Another experim ent confirmed the responsiveness of A/J mice exposed to ECS for 5 months, f ollowed by 4 months of recovery in air (75.0% vs. 25.0%, and 1.05 +/- 0.17 vs. 0.25 +/- 0.10). In contrast, the increase in lung tumor yield after exp osure to ECS for 2 months, followed by recovery in air for 7 months, was no t significant, and the continuous exposure to ECS for 9 months was totally ineffective. These data, in agreement with previous results of others, show that exposure of A/J mice to ECS for 5-6 months, followed by recovery in a ir for 4 months, is successful in inducing a weak but significant and repro ducible increase in lung tumor yield. Furthermore, the simultaneous exposur e to the light emitted by halogen quartz bulbs for 9 months and to ECS for 5 months, followed by 4 months in air, was again weakly tumorigenic (incide nce of 55.0% and multiplicity of 0.75 +/- 0.19), whereas exposure to both E CS and light for 9 months was devoid of effect. The whole-body exposure of A/J mice to MCS, 1 h a day for 5 months, or weekly i.p. injections of MCSC for 5 months, followed in both cases by 4 months of recovery in air, failed to enhance the lung tumor yield. The whole-body exposure of SKH-1 hairless mice to ECS for 6 months, followed by exposure to halogen light for 8 mont hs, resulted in the formation of multiple skin tumors but failed to produce lung tumors. The whole-body exposure of C57BL/6 mice to ECS for 6 months f ailed to induce any lung tumor but caused alopecia, gray hair, and hair bul b cell apoptosis, which were prevented by the oral administration of N-acet ylcysteine.