This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Parker, R. J. Articles by Reed, E. Search for Related Content PubMed PubMed Citation Articles by Parker, R. J. Articles by Reed, E.

Ormaplatin Sensitivity/Resistance in Human Ovarian Cancer Cells Made Resistant to Cisplatin

Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892

¹ To whom requests for reprints should be addressed, at Medicine Branch, National Cancer Institute, Building 10, Room 12N 226, 900 Rockville Pike, Bethesda, MD 20892.

The human ovarian cancer cell lines A2780 and A2780/CP70 were studied to investigate the cellular basis for their relative sensitivities to tetrachloro(DL-trans)-1,2-diamminecyclohexaneplatinum(IV) (ormaplatin). Cells were exposed to ormaplatin for 1 h in all experiments. As assessed by colony formation assays, the A2780/CP70 cell line [50% inhibitory dose (IC₅₀) = 3.6 µM] was 9.5-fold more resistant to ormaplatin than the A2780 cell line [IC₅₀ = 0.38 µM]. For cisplatin, the IC₅₀ doses were 40 and 3 µM, respectively. Both cell lines were treated with ormaplatin at doses ranging from 0.10 to 40 µM, for the purpose of studying drug accumulation and efflux, and DNA adduct formation and repair. When these cell lines were treated at their respective IC₅₀ doses, drug accumulation was greater in the resistant cells. When treated at equal µM doses, the sensitive cells formed 8-fold more DNA adduct than the resistant cells. When cells were treated with ormaplatin so as to achieve equivalent levels of platinum-DNA modification, sensitive cells removed 53% of the platinum-DNA damage in the first 6 h after drug exposure, compared to 68% in the resistant cells. We conclude that in human ovarian cancer cells made resistant to cisplatin, there is moderate cross-resistance to ormaplatin. This cross-resistance is not explained by differences in drug accumulation but is associated with reduced platinum-DNA adduct formation, which may be attributable in part to cytosolic inactivation of drug.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 5/11/92. Accepted 11/ 3/92.