Doxorubicin cytotoxicity to P388 lymphocytic leukemia as determined by alkaline elution and established assays.

Very large variations exist in the response of individual tumors to antineoplastic agents, even when the tumors are apparently very similar from the point of view of stage and histological classification. It has been recognized for a long time that methods capable of revealing the specific chemosensitivity of individual tumors could be useful for an individual optimization of a chemotherapeutic protocol. The Tumor Colony Forming Assay (TCFA) and the Biochemical Antimetabolic Assay (BAA) have been proposed for this purpose. Their main limitation is a consequence of the fact that the capability of in vitro growth is required from cells of a tumor grown in vivo. This is often lacking or very poor in the first in vitro passages. In this work we have investigated the possibility of using a sensitive method for evaluating DNA damage, the Alkaline Elution technique (AE). Cells treated in vivo can be easily tested directly for DNA damage. No cell proliferation in vitro is required. It is not required that the measured effect is the specific cause of cell death. A P388 Doxorubicin sensitive line and a resistant subline were tested. Correct correlations between DNA damage and chemosensitivity were obtained working both in vivo and in vitro. This test could be useful for assessing the chemosensitivity in vivo of alkylating and intercalating agents.