Potentiation of genomic instability with combined exposure of olaparib and cisplatin.

A. Dose-response curve of survival with cisplatin alone and cisplatin with 1μM olaparib of MCF-10A and primary T cell 1. In MCF-10A, cells were grown with indicated concentration of cisplatin for the first 30 hr with or without continuous exposure at 1 μM olaparib. Clonogenic survival was assessed by colony counting at 9 days. In primary T cell 1, cells were grown with indicated concentration of cisplatin with or without 1 μM olaparib for the first 24 hr. Viable cells were scored and enumerated by trypan blue exclusion at 7 days. Means with SD are shown (MCF-10A: n = 3, primary T cell 1: n = 2). B. Induction of SCEs by cisplatin and/or olaparib in MCF-10A and primary T cell 1. In MCF-10A, cells were exposed at 0.5 μM cisplatin with or without 1 μM olaparib for 30 hr. In primary T cell 1, cells were exposed at 0.5 μM cisplatin for the first 24hr with or without 1 μM olaparib for 70 hr. Fold increases of SCE per chromosome compared with no treatment or 0.5 μM cisplatin are shown for each cell type. Approximately 50 metaphases were counted for each cell. Error bars depict the mean with SD. Asterisks designate statistical significance for unpaired t-test at P < 0.0001. C. Chromatid-type aberrations following cisplatin with or without olaparib in primary T cell 1. Cells were exposed at 0.5 μM cisplatin with or without 1 μM olaparib for 24 hr. One hundred metaphases were counted for each exposure. Fold increases of chromatid-type aberrations per chromosome compared with no treatment or 0.5 μM cisplatin are shown for each cell type. The y-axis is the number of total chromatid-type aberrations per chromosome for each metaphase counted. Error bars indicate mean with SEM. The P-values were calculated using unpaired t-test.