Chemoresistance in rat ovarian tumours
Zeller, W.J.; Frühauf, S.; Chen, G.; Keppler, B.K.; Frei, E.; Kaufmann, M.
European Journal of Cancer 27(1): 62-67
1991
ISSN/ISBN: 0959-8049 PMID: 1826445 Document Number: 376541
In a cisplatin resistant subline (O-342/DPP) of an intraperitonally 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/106 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 sulphoxime 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 of 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.