Chemoresistance in rat ovarian tumours.
In a cisplatin resistant subline (O-342/DPP) of an intraperitoneally growing transplantable rat ovarian tumour (O-342), intracellular glutathione (GSH) was approximately doubled (mean [S.E.] 1.5 [0.26] vs. 0.8 [0.2] nmol/10(6) cells). GSH reductase activity was higher (30.64 [4.07] vs. 20 [0.92] nmol/min per mg protein), although no difference was found for GSH-S-transferase. 24 h after exposure to cisplatin, formation of DNA interstrand cross-links was at a maximum in both lines and significantly higher in O-342 (162 [23] vs. 88 [22] rad eq). Combination treatment of O-342/DDP with buthionine sulphoximine plus cisplatin resulted in a marginal increase in survival compared with cisplatin treatment; treatment of this line with 3-aminobenzamide plus cisplatin was also superior to cisplatin alone. In the sensitive line both combinations were likewise superior to cisplatin alone. In vitro, at equimolar concentration, a new platinum complex (CTDP) was at least as active as cisplatin in both lines, which suggests a superior therapeutic index because its LD50 in mice is threefold higher than that of cisplatin. A ruthenium complex (ICR) had a higher activity in the resistant line. A titanium complex (budotitane) was not active.
Zeller
W J
WJ
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Frühauf
S
S
Chen
G
G
Keppler
B K
BK
Frei
E
E
Kaufmann
M
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002460:Cell Line; D002945:Cisplatin / Q000627:therapeutic use*; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008670:Metals / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D008670:Metals; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin