Doxorubicin does not kill L929 cells at concentrations that profoundly reduce clonogenic survival. Instead, the cell and nuclear volume progressively increase for at least 1 week following drug exposure leading to the production of characteristic giant cells. The increase in nuclear volume is due to continued DNA synthesis and increase in chromosome number without entry into mitosis. The implications of this finding for in vitro chemosensitivity assays and for the mechanism of doxorubicin cytotoxicity are discussed.

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This work was supported in part by grants from the National Cancer Institute (CA41608) and the Research Foundation of SUNY.

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