Tobacco-specific carcinogens induce methylation, DNA adducts, DNA damage, and activation of DNMT1. Tobacco-specific carcinogens induce methylation, DNA.

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Tobacco-specific carcinogens induce methylation, DNA adducts, DNA damage, and activation of DNMT1. Tobacco-specific carcinogens induce methylation, DNA adducts, DNA damage, and activation of DNMT1. A, Heatmap of metabolites from J82 cells that were treated with NNK (100 μmol/L), BaP (10 μmol/L), with NNK followed by AZA (5 μmol/L; (NNK + AZA) and BaP + AZA (FDR < 0.25). B, DNA adducts in untreated and treated cells with NNK, BaP, NNK + AZA, and BaP + AZA were measured by LC/MS-MS (P < 0.005). C, Confocal microscopy and quantification analysis of γ-H2AX (green) in J82 cells treated with NNK, NNK + AZA, BaP, and BaP + AZA (P < 0.0001). D, Western blots and quantification of γ-H2AX protein levels in J82 cells treated with aphidicolin, NNK, and AZA (P < 0.0001). β-Actin was used as the loading control. Comparison of DNMT1 protein (E) and mRNA (F) expression in tissues of smokers (n = 15) and non-smokers (n = 15) and their quantification (P < 0.05). G, IHC analysis of DNMT1 expression in bladder cancer tissues from smoker and non-smoker. Feng Jin et al. Cancer Prev Res 2017;10:588-597 ©2017 by American Association for Cancer Research