Cyclophosphamide-induced cytogenetic effects in mouse bone marrow and spleen cells in in vivo and in vivo/in vitro assays.

Sister chromatid exchange (SCE) and chromosomal aberration studies have been used to monitor human populations for genotoxic exposure to chemical substances. These monitoring techniques involve collection of blood and/or bone marrow from the exposed subjects and culturing cells for one or two cell cycles with various treatments in culture. The results obtained from such in vivo/in vitro studies may lead to an over- or underestimation of the damage that could occur in vivo. In the present study, which uses a mouse model, the in vivo/in vitro cytogenetic assays (SCEs and chromosomal aberrations) have been compared with similar in vivo systems in bone marrow and spleen cells treated with various doses of cyclophosphamide (CPA). The results indicate a significant difference in CPA-induced cytogenetic endpoints between in vivo and in vivo/in vitro conditions in both organs. However, linear relationships were found between CPA dose and cytogenetic end point analyzed under both conditions. Based on these results it appears that the in vivo/in vitro assay is a useful technique for indicating potential in vivo damage of chemicals.