. 2011 Dec 13;41(1):79–105. doi: 10.1093/ije/dyr154

Table 1.

Effects of environmental chemicals on epigenetic changes

Environmental chemicals	Epigenetic changes	In vitro/in vivo	Tissue/species	Example of diseases potentially associated with the observed changes in epigenetic changes
Arsenic	DNA methylation
	Global hypomethylation	In vitro	Human HaCaT keratinocytes,⁸⁰ human prostate epithelial cell line RWPE-1,⁸¹^,⁸² TRL 1215 rat liver epithelial cell line,⁸³ V79-Cl3 Chinese hamster cells²²⁶	Various cancers^227–230 and schizophrenia²³¹
	Global hypomethylation	In vivo	129/SvJ mice,⁸⁴ fisher 344 Rat,⁸⁶ homozygous Tg.AC mice,⁸⁷ goldfish,²³² human PBL²³³	Various cancers^227–230 and schizophrenia²³¹
	Global hypomethylation and c-Ha-ras hypomethylation	In vivo	C57BL/6J mice⁸⁵	Various cancers^227–230 and schizophrenia²³¹
	Global hypermethylation	In vivo	Human PBL⁸⁸^,⁸⁹	Colorectal cancer,^234–236 renal cell carcinoma,²³⁷ acute lymphoblastic leukaemia²³⁸ and bladder urothelial cell carcinoma²³⁹
	DAPK hypermethylation	In vitro	Human uroepithelial SV-HUC-1 cells⁹⁰	Various cancers^240–251
	P16 hypermethylation	In vitro	Human myeloma cell line U266⁹¹	Various cancers²⁴¹^,²⁴⁸^,²⁵⁰^,^252–257
	DBC1, FAM83A, ZSCAN12 and C1QTNF6 hypermethylation	In vitro	Human UROtsa cells⁹²	Bladder cancer,²⁵⁸ breast cancer²⁵⁹ and malignant lymphoproliferative neoplasms²⁶⁰
	P53 hypermethylation	In vitro	Human lung adenocarcinoma A549 cells⁹³	Breast cancer²⁶¹ and hepatoblastoma²⁶²
	C-myc hypomethylation	In vitro	TRL 1215 rat liver epithelial cells⁹⁴	Gastric cancer,²⁶³^,²⁶⁴ colon cancer,²⁶³ liver cancer,²⁰⁷^,²⁶⁵^,²⁶⁶ kidney cancer²⁰⁷ and bladder cancer²⁶⁷
	C-myc and c-Ha-ras hypomethylation	In vitro	Syrian hamster embryo cells⁹⁵	Gastric cancer,²⁶³^,²⁶⁴ colon cancer,²⁶³ liver cancer,²⁰⁷^,²⁶⁵^,²⁶⁶ kidney cancer²⁰⁷ and bladder cancer²⁶⁷
	P16 and RASSF1 hypermethylation	In vivo	A/J mice⁹⁶	Various cancers²⁴¹^,²⁴⁸^,²⁵⁰^,^252–257^,²⁶⁸^,²⁶⁹
	Global hypomethylation and ER-alpha hypomethylation	In vivo	C3H mice⁹⁷	Various cancers⁹⁷^,^227–230 and schizophrenia²³¹
	P53 and P16 hypermethylation	In vivo	Human PBL⁹⁸	Various cancers²⁴¹^,²⁴⁸^,²⁵⁰^,^252–257^,²⁶¹^,²⁶²
	DAPK hypermethylation	In vivo	Human bladder, kidney and ureter⁹⁹	Various cancers^240–251
	RASSF1A and PRSS3 hypermethylation	In vivo	Human bladder¹⁰⁰	Lung cancer and prostate cancer²⁶⁸^,²⁶⁹
	P16 hypermethylation	In vivo	Human PBL²⁷⁰	Various cancers²⁴¹^,²⁴⁸^,²⁵⁰^,^252–257
	P53 hypermethylation	In vivo	Human basal cell carcinoma¹⁰²	Breast cancer²⁶¹ and hepatoblastoma²⁶²
	Both hypomethylation and hypermethylation of VHL	In vitro	Human kidney cells²⁷¹	Renal cell carcinoma²⁷¹
	Histone modification
	↓H3 acetylation	In vitro	UROtsa and URO-ASSC cells⁹²	Renal cell carcinomas²⁷²
	↓H4K16 acetylation	In vitro	UROtsa cells¹⁰⁴	Bladder cancer²⁷³
	↑H3K14 acetylation	In vitro	NB4 cells¹⁰⁵	Diabetic nephropathy²⁷⁴
	↑H3S10 phosphorylation	In vitro	NB4 cells¹⁰⁵	Diabetic nephropathy²⁷⁴
	↑H3 phosphorylation	In vitro	WI-38 human diploid fibroblast cells¹⁰⁶	Diabetic nephropathy²⁷⁴
	↑H3K9 acetylation	In vitro	HepG2 hepatocarcinoma cells¹⁰⁷	Diabetic nephropathy²⁷⁴
	↓H3, H4, H2a, H2b acetylation ↓H3 and H4 methylation	In vitro	Drosophila melanogaster tissue culture cell line KC161¹⁰³	Heart disease²⁷⁵ and traumatic brain injury²⁷⁶
	↑H2b methylation	In vitro	Drosophila melanogaster tissue culture cell line KC161¹⁰³	Heart disease²⁷⁵ and traumatic brain injury²⁷⁶
	↑H3K36 trimethylation	In vitro	Human lung carcinoma A549 cells¹¹⁰	Diabetic nephropathy,²⁷⁴ multiple myeloma²⁷⁷ and prostate cancer²⁷⁸
	↓H3K36 dimethylation
	↑H3K4 dimethylation
	↑H3K9 dimethylation	In vitro	Human lung carcinoma A549 cells¹¹⁰^,²⁷⁹	Prostate cancer,²⁷⁸ kidney cancer,²⁷⁸ lung cancer,²⁸⁰ HCC²⁸¹ and AML²⁸²
	↓H3K27 trimethylation
	↑H3K4 trimethylation
	↑H2AX phosphorylation	In vitro	RPMI7951 melanoma cells¹¹²	Ataxia telangiectasia²⁸³
	↓H3K18 acetylation	In vitro	1470.2 cell line derived from the mouse adenocarcinoma parent line²⁸⁴	Prostate cancer²⁷⁸ and colon cancer²⁸⁵
	↓H3R17 methylation	In vitro		Prostate cancer²⁷⁸ and colon cancer²⁸⁵
	miRNAs
	↑miR-222, ↓miR-210	In vitro	TK6 cell line¹⁰⁰	Various cancers^286–290 and AD²⁹¹
	↓miR-19a	In vitro	T24 cell line¹¹⁵	Various cancers^292–300
Nickel	DNA methylation
	ATF-1, HIF-1, gpt and Rb hypermethylation	In vitro	G12 cell line¹¹⁶^,¹¹⁷	Various cancers^301–306
	P16 hypermethylation	In vivo	Mouse histiocytomas¹¹⁹	Various cancers²⁴¹^,²⁴⁸^,²⁵⁰^,^252–257
	Histone modification
	↑H3K9 methylation	In vitro	Human lung carcinoma A549 cells¹²³^,³⁰⁷	Heart disease²⁷⁵ and traumatic brain injury²⁷⁶
	↓Ac at all four core histones	In vitro	Human lung carcinoma A549 cells¹²³^,³⁰⁷	Heart disease²⁷⁵ and traumatic brain injury²⁷⁶
	↑H3K9 dimethylation	In vitro	Human lung carcinoma A549 cells,¹²²^,¹²⁴ G12 cells,¹¹⁶^,¹²³^,¹²⁶^,¹²⁸^,²⁷⁹ 1HAEo- cell line,¹²⁰^,¹²¹ human (HAE) and rat (NRK) cells,¹²⁵ Chinese hamster cell line¹²⁷	Lung cancer,³⁰⁸ heart disease,²⁷⁵ chronic glomerular disease³⁰⁹ and traumatic brain injury²⁷⁶
	↑H2a, H2b ubiquitylation
	↓H3K4 methylation
	↓H3K4 acetylation
	↓H2a, H2b, H3, H4 acetylation
	↓H4K5, H4K8, H4K12, H4K16 acetylation	In vivo	Human lung carcinoma A549 cells¹³⁰	Ataxia telangiectasia³¹⁰
	↓H2A, H2B, H3, H4 acetylation (especially in H2BK12 and H2BK20)	In vitro	Human airway epithelial 1HAEo- (HAE) cell line¹³¹	Heart disease²⁷⁵ and traumatic brain injury²⁷⁶
	↑H3 phosphorylation	In vitro	Human lung carcinoma A549 cells¹³²	Diabetic nephropathy²⁷⁴
Cadmium	DNA methylation
	Global DNA hypomethylation	In vitro	K562 cell¹³³	Colorectal cancer,^234–236 renal cell carcinoma,²³⁷ acute lymphoblastic leukaemia,²³⁸ bladder urothelial cell carcinoma²³⁹
	Initially induces DNA hypomethylation, prolonged exposure results in DNA hypermethylation	In vitro	TRL1215 rat liver cells¹³⁴	Not applicable
	miRNAs
	↓miR-146a	In vivo	Human PBL¹³⁷	Various cancers^311–313
Chromium	DNA methylation
	P16 and hMLH1 hypermethylation	In vivo	Human lung¹⁴³^,¹⁴⁴	Various cancers²⁴¹^,²⁴⁸^,²⁵⁰^,^252–257^,^314–316
	Gpt hypermethylation	In vitro	G12 cell line³¹⁷	Not applicable
	Histone modification
	↓H3S-10 phosphorylation	In vitro	Human lung carcinoma A549 cells²⁷⁹	Type 2 diabetes,²⁷⁴ heart disease²⁷⁵ and traumatic brain injury²⁷⁶
	↓H3K4 trimethylation
	↓H3 and H4 acetylation ↑Dimethylation and trimethylation of H3K9 and H3K4
	↓H3K27trimethylation and H3R2 dimethylation
Aluminum	miRNAs
	↑miR-146a	In vitro	HN cells¹⁴⁹	AD,³¹⁸^,³¹⁹ cardiac hypertrophy³²⁰ and various cancers^321–328
	↑miR-9, -128, -125b	In vitro	HN cells³²⁹	AD,³³⁰ neurodegeneration³³¹ and various cancers^332–335
Mercury	DNA methylation
	Global hypomethylation	In vivo	Brain tissues in polar bear¹³⁹	Neurological disorders³³⁶^,³³⁷ and various cancer³³⁸
	Rnd2 hypermethylation	In vitro	Mouse embryonic stem cells¹⁴⁰	neuronal migration defect³³⁹
Lead	DNA methylation
Lead	Global hypomethylation	In vivo	Human PBL,¹⁴¹ newborn umbilical cord blood samples¹⁴²	Various cancers^227–230 and schizophrenia²³¹
Pesticides	DNA methylation
	P53 hypermethylation	In vitro	Human lung adenocarcinoma A549 cells⁹³	Breast cancer²⁶¹ and hepatoblastoma²⁶²
	Alter DNA methylation in the germ line	In vivo	Rat testis^154–156	Potential effects in the offspring
	Hypomethylation of c-jun and c-myc	In vivo	Mouse liver¹⁵⁸^,¹⁵⁹	Gastric cancer,²⁶³^,²⁶⁴ colon cancer,²⁶³ liver cancer,²⁰⁷^,²⁶⁵^,²⁶⁶ kidney cancer²⁰⁷ and bladder cancer²⁶⁷
	Global hypomethylation (Alu)	In vivo	Human PBL¹⁶¹^,¹⁶²	Various cancers^227–230 and schizophrenia²³¹
	Both hypomethylation and hypermethylation of VHL	In vitro	Human kidney cells²⁷¹	Renal cell carcinoma²⁷¹
	Histone modification
	↑Ac of H3 and H4	In vitro and in vivo	Immortalized rat mesencephalic/dopaminergic cells (N27 cells)¹⁶⁹	Parkinson’s disease¹⁶⁹
Air pollution	DNA methylation
	Global hypomethylation	In vivo	Human PBL⁸	Various cancers^227–230 and schizophrenia²³¹
	iNOS hypomethylation	In vivo	Human PBL¹⁷³	Lung cancer³⁴⁰
	Global hypermethylation	In vivo	C57BL/CBA mice sperm¹⁷⁴	Colorectal cancer,^234–236 renal cell carcinoma²³⁷, acute lymphoblastic leukaemia²³⁸ and bladder urothelial cell carcinoma²³⁹
	Hypermethylation of IFNg and hypomethylation of IL4	In vivo	CD4+ T lymphocytes¹⁷⁵	Asthma¹⁷⁵
	Histone modification
	↑H3K4 dimethylation and H3K9 acetylation	In vivo	Human PBL¹⁷⁷	Diabetic nephropathy²⁷⁴
	Global hypomethylation (Alu, LINE-1)	In vivo	Human buffy coat³¹⁷	Various cancers^227–230 and schizophrenia²³¹
	miRNAs
	↑miR-222	In vivo	Human PBL¹³⁷	Various cancers^286–288
	↑miR-21	In vivo	Human PBL¹³⁷	Various cancers²⁹⁹^,^341–347
Benzene	DNA methylation
	Global hypomethylation (Alu, LINE-1)	In vivo	Human PBL⁸	Various cancers^227–230 and schizophrenia²³¹
	P15 hypermethylation and melanoma antigen-1 (MAGE-1) hypomethylation	In vivo	Human PBL^165–168^,¹⁸⁶	Psoriasis³⁴⁸ and various cancers^349–360
	Global DNA hypomethylation	In vitro	Human lymphoblastoid cell line TK6¹⁸⁷	Various cancers^227–230 and schizophrenia²³¹
	Hypermethylation of poly (ADP-ribose) polymerases-1 (PARP-1)	In vitro	Lymphoblastoid cell line F32¹⁸⁸	Various cancers¹⁸⁸
Bisphenol A	DNA methylation
	Hypomethylation of the Agouti gene and CabpIAP	In vivo	Mouse embryo¹⁹²	Mice with hypomethylation of the Agouti gene are obese, diabetic and exhibit increased cancer rates³⁶¹^,³⁶²
	Hypomethylation of the homeobox gene Hoxa10	In vivo	CD-1 mice¹⁹⁴	Not applicable
	Hypermethylation of LAMP3^.	In vitro	Breast epithelial cells¹⁹⁵	Breast cancer¹⁹⁵
	miRNAs
	↑miR-146a	In vitro	3A placental cells¹⁹⁶	Cardiac hypertrophy,³²⁰ AD³¹⁸^,³¹⁹ and various cancers^321–328
Dioxin	DNA methylation
	Igf2 hypomethylation	In vivo	Rat liver¹⁹⁸	Russell–Silver syndrome^363–365 and various cancers^366–370
	Alterations in DNA methylation at multiple genomic regions	In vivo	Splenocyte of mice¹⁹⁹	Not applicable
	miRNAs
	↑miR-191	In vivo	Rat liver²⁰⁰	Breast cancer,³⁴² colorectal cancer³²¹^,³⁷¹ and gastric cancer³⁷²
RDX	miRNAs
	↑let-7, miR-15, -16, -26, -181 ↓miR-10b	In vivo	Mouse brain and liver²⁰²	Various cancers³²⁵^,^373–380
	↑miR-206, -30, -195	In vivo	Mouse brain and liver²⁰²	Various cancers³⁴²^,^381–385
DES	miRNAs
DES	↓miR-9-3	In vitro	Breast epithelial cells²⁰⁵	Breast cancer²⁰⁵
Drinking water	DNA methylation
Drinking water	Global hypomethylation c-myc hypomethylation	In vivo	Mice liver²⁰⁷^,²⁰⁸	Gastric cancer,²⁶³^,²⁶⁴ colon cancer,²⁶³ liver cancer,²⁰⁷^,²⁶⁵^,²⁶⁶ kidney cancer²⁰⁷ and bladder cancer²⁶⁷

PBL, peripheral blood leucocytes; HCC, hepatocellular carcinoma; AML, acute myeloid leukaemia; AD, Alzheimer’s disease; HN cells, human neural cells; RDX, hexahydro-1,3,5-trinitro-1,3,5-triazine; DES, diethylstilbestrol.