Relationship between the induction of chromosome damage and cytotoxicity for amsacrine and congeners.

The antitumor drug amsacrine causes chromosomal aberrations both in cultured cells (L1210 murine leukemia and HeLa cells) and in vivo (L1210 leukemia). The proportions of different types of aberrations, mainly chromatid gaps, chromatid exchanges, and acentric chromosome fragments, are similar in both the in vivo and in vitro experiments. A small proportion of cells, particularly after drug exposure for 24 hours, show extensively damaged or pulverized chromosomes. In in vitro experiments using HeLa cells and amsacrine together with two analogs of amsacrine with differing cytotoxic activity, an inverse relationship between the frequency of chromosomal aberrations and cell survival has been demonstrated. The results are consistent with the proposal that for this class of drugs, the induction of chromosomal aberrations, both in vivo and in vitro, leads to cell death.