Genotoxicity of Inhibitors of DNA Topoisomerases I (Camptothecin) and II (m-AMSA)In vivo and In vitro

摘要

The present study was designed to determine and compare the clastogenicity ofamsacrine and camptothecin in vivo in mouse bone marrow and peripheral blood lymphocytes and in vitro in mouse lymphoma L5178Y cells. It was expected that amsacrine, which interferes with topoisomerase II to induce double-strand DNA breaks, and camptothecin, which interferes with topoisomerase I to induce single-strand DNA breaks, would induce different types of chromosomal aberrations. However, both drugs produced quantitatively and qualitatively similar numbers and types of aberrations under similar experimental conditions. In mouse bone marrow, both drugs (3 mg/kg) induced about 30% damaged cells, with an average of 0.4 chromatid breaks per cell. Cell cycle specificity was indicated by the absence of chromosomal aberrations when exposure to the drugs occurred during GO in vivo. In vitro, amsacrine, and camptothecin induced 161 and 20 mutants/10 (to the sixth power) survivors/nM, respectively; they induced 6 and 2 aberrant cells/nM, respectively. In contrast to the in vivo results, the drugs induced high levels