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In Vitro Effects on DNA Synthesis as a Predictor of Biological Effect from Chemotherapy¹

Audie Murphy Veterans Administration Hospital and University of Texas Health Science Center at San Antonio, San Antonio, Texas [R. B. L., G. A. T.], and University of Texas System Cancer Center, Houston, Texas [L. K. H.]

Cell suspensions of tumor or normal bone marrow were incubated in vitro with control media (supplemented Ham's F-10 medium or autologous, pretreatment plasma) and with autologous, posttreatment plasma containing chemotherapeutic agents or their metabolites (treated plasma). Drug-specific perturbation of tumor cell DNA synthesis, as measured by the thymidine labeling index, occurred in treated plasma in 9 of 9 courses where antitumor effect was seen compared to 2 of 8 in which chemotherapy failed. Similar effects on myelocyte labeling index in normal marrow were observed in 14 of 20 courses associated with leukopenia and in 0 of 3 in which there was none. The labeling index was affected in 23 of 29 courses with associated biological effect (79%) versus 2 of 11 courses without biological effect (p = 0.0007). Measurement of changes in labeling index upon exposure to drug-containing plasma may become a useful guide to the choice of antineoplastic chemotherapy.

¹ Supported by the Veterans Administration.

² Present address: Department of Hematology-Oncology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106. To whom requests for reprints should be addressed.

Received 1/14/80. Accepted 4/ 7/80.