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Selenium (Se) Cytotoxicity in Drug Sensitive and Drug Resistant Murine Tumour

1995; Mary Ann Liebert, Inc.; Volume: 10; Issue: 3 Linguagem: Inglês

10.1089/cbr.1995.10.243

2332-4953

Joshua M. Shallom, Aarti Juvekar, M.P. Chitnis,

DNA Repair Mechanisms

Selenium is known to inhibit growth rate of neoplastic cells. We have investigated the role of selenium (Se) in resensitization of the adriamycin (ADR) resistant murine P388/ADR cells to the action of ADR. The experiments were performed in the ADR sensitive parental P388 murine leukemia (P388/S) and its subline P388/ADR, resistant to ADR, developed in our laboratory. The effect of Se was observed to be dose dependent i.e. Se at a concentration of 5x10-8M resulted in potentiation of DNA biosynthesis whereas 5x10-6M and 5x10-5M Se resulted in inhibition of DNA-biosynthesis in P388/S cells. Along with ADR there was a further increase in inhibition of DNA biosynthesis. In P388/ADR cells, Se at 5x10-6M and 5x10-8M concentration resulted in inhibition of DNA biosynthesis, which increased further when combined with ADR indicating resensitization of these cells to the action of ADR. The inhibition was observed to be partially irreversible. These results were further confirmed in the in vivo and in vitro bioassays where the Se and Se+ADR treatments resulted in increased lifespan of tumor bearing mice.