Figure 4.
Both bendamustine (BEN) and 4-hydroperoxycyclophophamide (4-HC) have additive effect with CNDAC in HR deficient cells. A, CHO cell lines wild-type (WT1), deficient in XRCC3 (−XRCC3) and complemented with XRCC3 (+XRCC3) were treated concomitantly with BEN (2 – 20 µM) and CNDAC (0.002 – 0.02 µM) for 24 hours before washout. Colonies formed were quantitated and clonogenicity of all three lines were compared for treatment with bendamustine alone vs bendamustine-CNDAC combination at a fixed ratio (1000:1). B, CHO cell lines wild-type (WT1), deficient in RAD51D (−RAD51D) and complemented with RAD51D (+RAD51D) were treated concomitantly with BEN (2 – 30 µM) and CNDAC (0.002 – 0.03 µM) as in A. Clonogenicity of all three lines were compared for treatment with bendamustine alone vs bendamustine-CNDAC combination at a fixed ratio (1000:1). C, Chinese hamster wild-type line WT2 and BRCA2 deficient line (−BRCA2) were exposed to CNDAC (0.002 – 0.02 µM) subsequent to addition of 4-HC (0.008 – 0.08 µM) and incubated for 24 hours before washout. Clonogenicity of all three lines were compared for treatment with bendamustine alone vs bendamustine-CNDAC combination at a fixed ratio (4:1). D, CHO cells deficient in XRCC3 (−XRCC3) and complemented with XRCC3 (+XRCC3) were treated concomitantly with CNDAC (0.002 – 0.012 µM) and 4-HC (0.032 – 0.192 µM) for 24 hours. Clonogenicity of all three lines were compared for treatment with bendamustine alone vs bendamustine-CNDAC combination at a fixed ratio (16:1). CIs of respective deficient cell lines in A - D are listed below the plots.