In vivo oxygen consumption rate of DS sarcoma cells on inhibition of DNA synthesis.
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.
Thews
O
O
Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, Mainz, Germany.
Kelleher
D K
DK
Vaupel
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001201:Ascites / Q000209:etiology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D003864:Depression, Chemical; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012513:Sarcoma, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D008148:Lovastatin; D014740:Vidarabine; C024352:fludarabine