TREATMENT OF HUMAN OVARIAN TUMOR XENOGRAFTS WITH SELENITE PREVENTS THE MELPHALAN-INDUCED DEVELOPMENT OF DRUG-RESISTANCE

Human ovarian tumors (derived from A2780 cells), growing as subcutaneo us xenografts in immunodeficient mice, develop melphalan-resistant cel ls after a single treatment of the tumor-bearing animal with the drug [Caffrey, Zhang and Frenkel, submitted for publication]. Treatment of the animals with selenite by ip. injection prevented the development o f primary resistance to melphalan as well as cross-resistance to cispl atin. Selenite treatment also prevented the melphalan-induced increase in the cellular level of glutathione. In contrast, selenite administe red s.c. or in drinking water had relatively little effect on the deve lopment of resistance. The results in this animal model suggest that s elenite may be clinically useful in preventing the development of drug resistance during chemotherapy of cancer.