DNMT inhibitor dosing schedule Cell type or specie PAH type Effect DNA methylation status Source Human cell adenocarcinoma, A549 BaP 1 nM, 100 nM, and 10 uM hCYP1A1 expression started with 10 μ M.hCYP1A1 expression started with 100 nM.35% complete methylation [65 ] 5AzadC, 5 uM, 96 h Human breast carcinoma cell line, MCF-7 10 nM TCDD lasts 24 hours hCYP1A1 expression increased 2-3-fold in Aza versus ctrl but did not change in Aza-TCDD versus TCDD.hCYP1A1 expression increased 4-fold in Aza versus ctrl and 7-fold in Aza-TCDD versus ctrl.Both cell lines: highly methylated at CpG sites in enhancer region. Low methylated at CpG sites in promoter region. [66 ] 5AzadC, 0, 0.25, and 1 uM Human prostatic epithelial cell line, PWR1-E TCDD, 10 nM hCYP1A1 expression increased in both PWR1 and RWPE1 treated with AzadC but not in the induction by TCDD.RWP1 low methylated than LNCaP at enhancer region. No methylation at promoter. [27 ] Human prostate adenocarcinoma cell line, LNCaP LNCaP increased their hCYP1A1 induction by TCDD in a dose dependence of AzadC 5AzadC, 2 uM, 72 h (each 12 h) Mouse hepatoma cell line, Hepa1c1c7 5 uM BaP, 8 h Aza does not change mCYP1A1 expression versus controlmCyp1a1 induction versus BaP ND [28 ] 5AzadC, 5 uM, 3 days Mouse hepatoma cell line, Hepa1c1c7 10 nM TCDD, 48 h Nonincrease mCyp1a1 expression in Aza-TCDD induced versus TCDD.mCyp1a1 expression increased in Aza-TCDD induced versus TCDD. ND [67 ] 5AzadC, 5 uM, 72 h Human breast cancer cell line, MCF7 TCDD last 24 h of 5AzadC treatment MCF7, no differences. ND [29 ] 5AzadC 1, 5, 10, 50, 250, and 500 uM, 72 hours after EGF treatment Primary rat hepatocytes (Sprague-Dawley rats) rCYP1A1 protein increases in dose dependence of AzadC ND [68 ] 5AzadC, 0.5 uM, 5 days Primary normal human bronchial epithelial cells, NHBE ( AzadC increased hCYP1A1 expression in HLAC NHBE and HBEC were low methylated than HLAC at enhancer region. [69 ] 5AzadC, 5 uM, 7 days (with culture media changed on day four). On day 6 cells were split into 60 mm dishes in culture media with AzadC. Day 7, media were changed. Human cervical adenocarcinoma cell line, HeLa AzadC increased hCYP1A1 expression versus ctrl. HeLa and HepG2 were equally methylated at promoter. [70 ] 5AzadC, 5 μ M, 5 daysμ M RG108, 5 days Human primary hepatocytes (hPH) hESC-Hep: increased hCYP1A1 expression in both 5AzadC and RG108 treatments. hPH: no methylated [71 ] HDAC inhibitor dosing schedule Cell line type AHR ligand Effect Source TSA (200 ng/mL), 30 min prior to TCDD Mouse hepatoma cell line, Hepa1c1c7 TCDD, 1 pM No effect on EROD basal enzyme activity [72 ] TSA, 100 ng/mL, 24 h Human breast carcinoma cell line, MCF-7 TCDD 10 nM (after TSA), 24 h Increased basal hCYP1A1 expression, but TSA had no effect on TCDD induced mRNA.hCYP1A1 mRNA [66 ] SAHA (0.2–4.0 μ M),12 and 24 hμ M), 12 and 24 h Human breast carcinoma cell line, MCF-7 BaP, 4 μ M Increased BaP induced EROD activity and basal hCYP1A1 mRNAhCYP1A1 mRNAhCYP1A1 mRNAhCYP1A1 mRNA [73 ] TSA (25 μ M), 2, 4, and 7 days Primary rat hepatocytes (Sprague Dawley) None Increased EROD activity at day 7.rCYP1A1 mRNA at days 4 and 7. [74 ] Sodium butyrate (NaB), 2 mM,16 h Mouse hepatoma cell line, Hepa1c1c7 BaP, 5 μ M, 8 h No changes on basal and induced mCyp1a1 mRNA [28 ] TSA, 100 nM, 24 h Mouse hepatoma cell line, Hepa1-OT TCDD, 10 nM, 24 h Increased TCDD induced mCyp1a1 mRNAmCyp1a1 mRNA [67 ] AN-8 (1–5 μ M), 72 h Primary hepatocytes culture None Increased CYP1A1 protein level [68 ] TSA 250 nM,16 h Human cervical adenocarcinoma cell line, HeLa PCB, 136 3 μ M (after TSA), 6 h Increased basal and PCB induced hCYP1A1 mRNA [70 ]
