Table 1.

Effect of DNA methyltransferases and histone deacetylases inhibition on CYP1A1 expression.

DNMT inhibitor dosing schedule	Cell type or specie	PAH type	Effect	DNA methylation status	Source
	Human cell adenocarcinoma, A549 Human bronchial epithelium cell line, Beas-2B	BaP 1 nM, 100 nM, and 10 uM	hCYP1A1 expression started with 10 μM. hCYP1A1 expression started with 100 nM.	35% complete methylation 11% complete methylation.	[65]
5AzadC, 5 uM, 96 h	Human breast carcinoma cell line, MCF-7 Human cervical adenocarcinoma cell line, HeLa	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 Human prostatic epithelial cell line, RWPE-1	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 control Aza-BaP does not change mCyp1a1 induction versus BaP	ND	[28]
5AzadC, 5 uM, 3 days	Mouse hepatoma cell line, Hepa1c1c7 Mouse embryonic fibroblast, C3H10T1/2	10 nM TCDD, 48 h	Nonincrease mCyp1a1 expression in Aza-TCDD induced versus TCDD. C3H10T1: mCyp1a1 expression increased in Aza-TCDD induced versus TCDD.	ND	[67]
5AzadC, 5 uM, 72 h	Human breast cancer cell line, MCF7 Human hepatic cancer cell line, HepG2	TCDD last 24 h of 5AzadC treatment	MCF7, no differences. HepaG2. 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 (n = 12). Human bronchial epithelial cell lines (HBEC n = 3). Human lung adenocarcinoma cell lines (HLAC n = 9)		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 μM, 5 days 5 μM RG108, 5 days	Human primary hepatocytes (hPH) Human embryonic stem cells derived hepatocytes (hESC.Hep)		hESC-Hep: increased hCYP1A1 expression in both 5AzadC and RG108 treatments.	hPH: no methylated hESC-Hep: high 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 Increased TCDD, concentration dependence induction of EROD enzyme activity and CYP1A1 protein		[72]
TSA, 100 ng/mL, 24 h	Human breast carcinoma cell line, MCF-7 Human cervical adenocarcinoma cell line, HeLa	TCDD 10 nM (after TSA), 24 h	Increased basal hCYP1A1 expression, but TSA had no effect on TCDD induced mRNA. Increased basal and TCDD induced hCYP1A1 mRNA		[66]
SAHA (0.2–4.0 μM),12 and 24 h TSA (0.2–4.0 μM), 12 and 24 h	Human breast carcinoma cell line, MCF-7	BaP, 4 μM	Increased BaP induced EROD activity and basal hCYP1A1 mRNA No effects on BaP induced hCYP1A1 mRNA Increased BaP induced EROD activity and basal hCYP1A1 mRNA Decreased BaP induced hCYP1A1 mRNA		[73]
TSA (25 μM), 2, 4, and 7 days	Primary rat hepatocytes (Sprague Dawley)	None	Increased EROD activity at day 7. Increased rCYP1A1 protein at all days tested. Increased rCYP1A1 mRNA at days 4 and 7.		[74]
Sodium butyrate (NaB), 2 mM,16 h	Mouse hepatoma cell line, Hepa1c1c7	BaP, 5 μM, 8 h	No changes on basal and induced mCyp1a1 mRNA		[28]
TSA, 100 nM, 24 h	Mouse hepatoma cell line, Hepa1-OT Mouse embryonic fibroblast cell line, C3H10T1/2	TCDD, 10 nM, 24 h	Increased TCDD induced mCyp1a1 mRNA Increased TCDD induced mCyp1a1 mRNA		[67]
AN-8 (1–5 μM), 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 μM (after TSA), 6 h	Increased basal and PCB induced hCYP1A1 mRNA		[70]

ND: nondetermined. All increases or decreases in DNA methylation, mRNA, or protein were significantly different with respect to the respective control. For more information about this, references to the original work are provided.

EROD: Ethoxyresorufin O-deethylation CYP1A1 enzyme activity.