Genotoxic changes in the pulmonary alveolar macrophages of mice, rats and hamsters treated with tobacco smoke

To determine whether tobacco smoke (TS) is genotoxic for lung tissue macrophages (pulmonary alveolar macrophages, PAM) as a general result of its inhalatory action BD6 rats, Syrian golden hamsters and BDF1 (C57BlxDBA2) mice were subjected to wholebody exposure for 90 or 60 min daily (600 cm3 mainstream smoke in 16-1 glass chamber, 9 or 6 exposures of 15 min each, respectively), for different periods ranging up to 30 days. A significant enhancement of the frequency of polynucleated macrophages (BiN PAM) was observed in all animal species after more than 10-days of repeated exposure to TS. The increased level of BiN PAM (the number of bi- + poly-nucleated PAM) correlates with the duration of exposure to TS: on day 20 after the start of inhalation, more than 25‰ of mice PAM were polynucleated, while on day 30 this applied to approximately 50‰. Furthermore, a highly significant increase in the level of micronucleated PAM (MN PAM) was also established after 10 days TS treatment of mice and persisted to the end of these examinations. TS was effective in enhancing the micronucleated and polynucleated PAM levels in hamsters irrespective of their sex, as it was in male BD6 rats aged 2 or 11 months. It appears that TS induces a more pronounced elevation of polynucleated PAM frequency in rats than in hamsters and mice. These data suggest that inhaled TS is genotoxic in alveolar macrophages in all exposed species of laboratory animals. An attempt was made to trace the possible clastogenic effect of a single i.p. administration of cyclophosphamide (CP, 15 mg/kg) in mice simultaneously in bone marrow and in PAM. A definite clastogenic effect in bone marrow 24 h and 48 h after CP injection and a total absence of changes in PAM from the lungs during the 15-day period after clastogen exposure were established. These data may support the hypothesis of local production of PAM in the lung from their proliferative precursor. The results provide evidence that PAM in laboratory animals are a sensitive and useful target for assessing harmful effects associated with environmental chemical factors that can be inhaled, including TS.