Less than additive interaction between cigarette smoke and chromium(VI) ininducing clastogenic damage in rodents

A combination of tobacco smoking with certain agents has been shown to exer t synergistic carcinogenic effects. On the other hand, antagonism betweeen smoke and other pulmonary carcinogens has also been documented by both epid emiological and experimental data. In spite of a very large number of studi es carried out for decades in workers exposed to hexavalent chromium, the i nfluence of smoking habits on lung carcinogenesis induced by this metal has not been clarified. For this reason, we performed two studies evaluating c lastogenic effects in rodents. In the first one, BDF1 mice were exposed who le-body to mainstream cigarette smoke for 5 days and, on the last day, they received an i.p. injection of potassium dichromate. In the second study, S prague-Dawley rats were exposed whole-body to environmental cigarette smoke for 18 consecutive days and for the same period of time they received dail y intra-tracheal instillations of sodium dichromate. Individually, the two hexavalent chromium salts and cigarette smoke, either mainstream or environ mental, enhanced the frequency of micronuclei in bone marrow polychromatic erythrocytes of both mice and rats. Moreover, individual exposure to either environmental cigarette smoke or sodium dichromate enhanced the frequency of micronuclei and multiple nuclei in pulmonary alveolar macrophages of rat s. In both studies, combined exposure to cigarette smoke and hexavalent chr omium produced less than additive clastogenic effects. These results are co nsistent with our previous data, showing that hexavalent chromium and eithe r benzo[a]pyrene or cigarette smoke condensate behave antagonistically in i n vitro mutagenicity test systems and that the chromium reducing capacity o f human pulmonary alveolar macrophages and peripheral lung parenchyma is en hanced in smokers. Taken together, in the absence of any epidemiological ev idence, these findings rule out any occurrence of synergism between cigaret te smoke and hexavalent chromium, at least in certain stages of the carcino genesis process.