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Title: Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium

Abstract

Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the Earth's crust. A common route of human exposure is via diet and cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24 h; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181 genes, respectively. The genes most upregulated by acute exposure included several metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated following chronic exposure included the transcriptional regulator early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and urological diseases/cancer. Many of the dysregulatedmore » genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in carcinogenesis. In addition to gene expression changes, HepG2 cells treated with cadmium for 24 h indicated a reduction in global levels of histone methylation and acetylation that persisted 72 h post-treatment. - Highlights: • A common route of human exposure to the carcinogenic metal cadmium is via diet. • HepG2 cells were treated acutely or chronically with varying doses of cadmium. • Gene expression analysis was performed using Affymetrix Human Gene 1.0 Arrays. • Acute and chronic exposures altered the expression of 333 and 181 genes, respectively. • Acute cadmium exposure altered global levels of histone methylation and acetylation.« less

Authors:
; ; ;  [1];  [2];  [1]
  1. Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States)
  2. Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY (United States)
Publication Date:
OSTI Identifier:
22687799
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 288; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLATION; ACUTE EXPOSURE; APOPTOSIS; BIOSYNTHESIS; CADMIUM; CARCINOGENESIS; CARCINOGENS; CELL CYCLE; CHRONIC EXPOSURE; DIET; GENES; HEPATOMAS; HISTONES; KIDNEYS; LIPIDS; LIVER; METABOLISM; METALLOTHIONEIN; METHYLATION; MORPHOLOGY; PLANT GROWTH

Citation Formats

Cartularo, Laura, Laulicht, Freda, Sun, Hong, Kluz, Thomas, Freedman, Jonathan H., and Costa, Max. Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.08.011.
Cartularo, Laura, Laulicht, Freda, Sun, Hong, Kluz, Thomas, Freedman, Jonathan H., & Costa, Max. Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium. United States. https://doi.org/10.1016/J.TAAP.2015.08.011
Cartularo, Laura, Laulicht, Freda, Sun, Hong, Kluz, Thomas, Freedman, Jonathan H., and Costa, Max. 2015. "Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium". United States. https://doi.org/10.1016/J.TAAP.2015.08.011.
@article{osti_22687799,
title = {Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium},
author = {Cartularo, Laura and Laulicht, Freda and Sun, Hong and Kluz, Thomas and Freedman, Jonathan H. and Costa, Max},
abstractNote = {Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the Earth's crust. A common route of human exposure is via diet and cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24 h; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181 genes, respectively. The genes most upregulated by acute exposure included several metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated following chronic exposure included the transcriptional regulator early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and urological diseases/cancer. Many of the dysregulated genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in carcinogenesis. In addition to gene expression changes, HepG2 cells treated with cadmium for 24 h indicated a reduction in global levels of histone methylation and acetylation that persisted 72 h post-treatment. - Highlights: • A common route of human exposure to the carcinogenic metal cadmium is via diet. • HepG2 cells were treated acutely or chronically with varying doses of cadmium. • Gene expression analysis was performed using Affymetrix Human Gene 1.0 Arrays. • Acute and chronic exposures altered the expression of 333 and 181 genes, respectively. • Acute cadmium exposure altered global levels of histone methylation and acetylation.},
doi = {10.1016/J.TAAP.2015.08.011},
url = {https://www.osti.gov/biblio/22687799}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 288,
place = {United States},
year = {Sun Nov 01 00:00:00 EDT 2015},
month = {Sun Nov 01 00:00:00 EDT 2015}
}