Figure 3.

Temozolomide and CNDAC are synergistic in HR deficient CHO lines. A and B, CHO wild-type (WT1), XRCC3 deficient (−XRCC3) and XRCC3 complemented (+XRCC3) cells were exposed to temozolomide (1.2 – 10 µM) and CNDAC (0.002 – 0.02 µM) concomitantly for 24 hours before washout and colony formation. A, the colonies were quantitated and clonogenicity of all three lines were compared for treatment with temozolomide alone vs temozolomide-CNDAC combination at a fixed ratio (600:1). B, median effect analysis algebraic estimate of temozolomide-CNDAC combination, CIs and DRI at 90% clonogenic inhibition of the XRCC3 deficient line. C and D, CHO wild-type (WT1), RAD51D deficient line (−RAD51D) and RAD51D complemented lines (+RAD51D) were treated as in A and B. Concentrations of temozolomide tested in all lines were 0.7 – 10 µM, while concentrations of CNDAC were 0.002 – 0.03 µM. C, clonogenicity of all three lines were compared for treatment with temozolomide alone vs temozolomide-CNDAC combination at a fixed ratio (350:1). D, median effect analysis algebraic estimate of temozolomide-CNDAC combination, CIs and DRI at 90% clonogenic inhibition of the RAD51D deficient line. E and F, Chinese hamster wild-type (WT3) and BRCA2 deficient (−BRCA2) cells were exposed to temozolomide (4.8 – 10.8 µM) and CNDAC (4 – 9 nM) concomitantly for 24 hours before washout and colony formation. E, clonogenicity of both lines were compared for treatment with temozolomide alone vs temozolomide-CNDAC combination at a fixed ratio (1200:1). F, median effect analysis algebraic estimate of temozolomide-CNDAC combination, CIs and DRI at 90% clonogenic inhibition of the BRCA2 deficient line (mean of two experiments).