INHIBITION OF DNA-REPAIR AND SENSITIZATION OF CISPLATIN IN HUMAN OVARIAN-CARCINOMA CELLS BY INTERLEUKIN-1-ALPHA

Interleukin-1α induced an increase in both the cellular accumulation of cis-diamminedichloroplatinum (II) (cisplatin) and DNA platination and significantly reduced the removal of platinum from DNA of human ovarian (NIH: OVCAR-3) carcinoma cells in culture. The combinations of IL-1α and cisplatin were highly synergistic against these ovarian carcinoma cells and maximum levels of sensitization (15-20-fold) were observed during simultaneous exposure of cisplatin and IL-1α. IL-1α specific receptor antagonist decreased this synergy. These results strongly indicate that IL-1α inhibits DNA repair, and this inhibition of DNA repair may explain, in part, a strong synergistic interaction between IL-1α and cisplatin NIH: OVCAR-3 cells. © 1993 Academic Press, Inc.