Comparison of micronucleus formation in mouse bone marrow and spleen

The frequencies of micronucleated erythrocytes were compared in bone marrow and spleen of mice killed 24 and 48 h after a single i.p. dose of one directly acting carcinogen, N-nitroso-N-ethylurea (NEU, 100 mg/kg), and two indirectly acting ones, N-nitrosodimethylamine (NDMA, 50 mg/kg) and 7,12-dimethylbenz[a]anthracene (7,12-DMBA, 50 mg/kg). The treated/control ratio of the incidence of micronucleated polychromatic erythrocytes (MnPCEs) was similar in the two tissues for NDMA at 24 h (sampling at 48 h was precluded by toxicity) and for 7,12-DMBA at 48 h, while it was higher in the bone marrow than in the spleen for NEU at both 24 and 48 h and for 7,12-DMBA at 24 h. Concerning micronucleated normochromatic erythrocytes (MnNCEs), their frequency in both tissues was always lower than that of MnPCEs; however, while in bone marrow a marked increase in their incidence was induced by NEU and 7,12-DMBA, any response was absent in spleen, thus suggesting that this organ does not sequester micronucleated erythrocytes. These results already indicate that the spleen is not a useful alternative to the bone marrow in the micronucleus assay. Moreover, counting of MnPCEs in the spleen is made more difficult and prone to error by the low frequency of PCEs, and by their greater toxicity-induced reduction. This last effect was found to be enhanced by the use of old mice.