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In Vivo Oxygen Consumption Rate of DS Sarcoma Cells on Inhibition of DNA Synthesis¹

Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, D-55099 Mainz, Germany

The effect of inhibiting DNA synthesis on the cellular O₂ consumption rate of tumor cells (DS sarcoma) in vivo was analyzed using a photometric technique. Five days after DS-sarcoma ascites was induced in SD rats, animals were treated either with fludarabine (400 mg/kg i.p., 6 h prior to measurements) or lovastatin (3 x 20 mg/kg i.p., 24, 15, and 3 h prior to measurements), drugs that can inhibit tumor cell proliferation. In addition to cellular O₂ consumption, the cell cycle distribution and the fraction of DNA-synthesizing cells in the tumor ascites were measured. Both drugs lowered DNA synthesis significantly, an effect that was more pronounced with fludarabine. The cellular O₂ consumption rate following lovastatin application was significantly impaired (approximately 33%), whereas fludarabine had practically no effect on the respiration rate of tumor cells. From these data, it is concluded that a reduction in DNA synthesis does not necessarily result in a decrease in the O₂ consumption rate of tumor cells in vivo.

¹ This study was supported by Deutsche Krebshilfe Grant M 40/91 Va 1.

² To whom requests for reprints should be addressed, at Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, D-55099 Mainz, Germany. Pone: +49-6131-39-5209; Fax: +49-6131-39-5574.

Received 1/29/96. Accepted 3/18/96.