Interstrand crosslinks formation/repair, γH2AX and Rad51 foci formation, and melphalan toxicity in MM cell lines. (A) Representative autoradiograms for the Southern blot analysis of ICLs 0 to 48 hours after treatment with melphalan alone. DS, double-stranded DNA; SS, denatured, single-stranded DNA. (B) The kinetics of ICL formation and repair 2 to 48 hours after treatment with melphalan alone. NO INH, no inhibitor. The formation and repair of ICLs 2 to 48 hours after treatment of RPMI 8226 (C) or LR5 (D) cells with melphalan in the presence or not of an inhibitor. (E) Total amounts of ICLs, expressed as AUC, after treatment with melphalan in the presence or not of an inhibitor. (F) γH2AX foci formation 2 to 48 hours after treatment with melphalan alone. The formation of γH2AX foci after treatment of RPMI 8226 (G) or LR5 (H) cells with melphalan alone or in combination with an inhibitor. (I) Total amounts of γH2AX foci, expressed as AUC, after treatment with melphalan in the presence or not of an inhibitor. (J) Rad51 foci formation 2 to 48 hours after treatment with melphalan alone. Formation of Rad51 foci after treatment of RPMI 8226 (K) or LR5 (L) cells with melphalan alone or in combination with an inhibitor. (M) Total amounts of Rad51 foci, expressed as AUC, after treatment with melphalan in the presence or not of an inhibitor. (N) The induction of apoptosis 24 hours after treatment with melphalan in the presence or not of an inhibitor. (O) Correlation between the melphalan doses required for the induction of apoptosis and the drug-induced γH2AX foci in the same cells. The experiments shown were based on a minimum of 3 independent repeats. Bar graph and error bars show mean ± SD.