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. Author manuscript; available in PMC: 2014 Feb 1.
Published in final edited form as: Exp Hematol. 2012 Oct 17;41(2):180–188.e4. doi: 10.1016/j.exphem.2012.10.007

Figure 4.

Figure 4

Chk1 inhibition enhances FdUMP[10]-induced DNA damage. DNA histograms and Comet assays for HL60 cells treated with FdUMP [10] (Fd) for the indicated times. (A) Chk1 inhibition (SB218078 5 γmol/L) reduces viability of FUMP[10]-treated cells. The combination (FdUMP[10]/Chk1i) was significantly more cytotoxic than either single agent at both 24 (p < 0.0004) and 48 hours (p < 0.0001) based on six experiments in triplicate. (B) Effects of Chk1 inhibition in combination with FdUMP[10] (10 nmol/L, 48 hours) on cell-cycle progression. FdUMP[10] treatment results in S-phase arrest after one replicative cycle (<18 hours). The combination of FdUMP[10] and the Chk1 inhibitor SB218078 for 48 hours results in fewer arrested cells and greater sub-G0 fraction. (C) Comet assays under neutral conditions indicated that FdUMP[10] induced DNA strand breaks and that Chk1 inhibition substantially enhances FdUMP[10]-induced DNA damage. Tail moments (TM = Tail length × % of DNA in the tail) were calculated from 20 individually imaged cells from parameters measured by computer software (Loats Associates). FdUMP[10] + Chk1i vs. FdUMP[10] p < 0.000004.