The genotoxic and cytotoxic effects of nicotine in the mouse bone marrow

The objective of the present study was to investigate the potential of nicotine to induce micronucleated polychromatic erythrocytes (MNPCE) in bone marrow of male and female mice. Cyclophosphamide at 40 mg/kg was used as positive control clastogen. Single doses of 4, 8 or 16 mg/kg nicotine were given via oral intubation and bone marrow was sampled at 18, 24, 30, 36 and 48 h after treatment. Cyclophosphamide yielded the expected positive results. Despite the evident signs of acute toxicity shown by the animals, mainly at the 8 and 16 mg/kg doses of nicotine, and the reduction in the % PCE, the results show that the MNPCE frequency in male and female mice was not affected by treatment with any of the selected doses of nicotine, in either of the sampling times 18 or 24 h. However, at 30 and 36 h after treatment, the MNPCE showed significant increases in both genders after doses of 8 and 16 mg/kg. A sex-dependent response was recorded, with males having more MNPCE than females after treatment with 8 or 16 mg/kg nicotine and sampling at 30 h. However, at 36 h more MNPCE were induced in females than in males, suggesting different degrees of dose interaction in the sexes under the conditions of the assay. The response was directly correlated with bone-marrow toxicity, as greater bone-marrow suppression was noted in females than in males when 36 h samples were examined. By 48 h recovery was observed even though the cytotoxicity was high. These findings suggest that nicotine at high doses and after prolonged time intervals is genotoxic and cytotoxic for mouse bone marrow. (c) 2007 Elsevier B.V. All rights reserved.