DNA damage response to 5-azadC, as monitored by quantitative Western blotting, and the role of DNMT1 and DNMT3B. (A) The HCT116 cell lines indicated at the bottom of the Western panel were treated with 10 μM 5-azadC for 0, 24, 48, and 72 h (with fresh drug added every 24 h), and whole-cell extracts were prepared. Equal microgram amounts of extract were loaded onto SDS-PAGE gels, transferred to polyvinylidene difluoride membrane, and probed with the antibodies indicated at the right. Note that all cell lines and treatments were run on gels, probed with antibody, and exposed to film at the same time to allow for accurate and quantitative comparison between cell lines for a given antibody. GAPDH served as a loading control. (B) HCT116 cells untreated or treated with 10 μM 5-azadC (aza) for 48 h or 10 μg/ml bleomycin (bleo) for 4 h. (C) ATM-deficient cells show induction of the active phosphorylated form of CHK1 (phospho-Ser317) in response to 5-azadC treatment (10 μM), demonstrating involvement of the ATR pathway in response to 5-azadC-mediated DNA damage. Equal microgram amounts of whole-cell extract from EBS and YZ5 cells treated with 5-azadC for 0, 24, 48, and 72 h were used as described in panel A. pS, phospho-serine; pT, phospho-threonine. Hrs tx, hours of treatment; untx, untreated.