title: Gene expression profiling to identify the toxicities and potentially relevant human disease outcomes associated with environmental heavy metal exposure.
abstract: Heavy metals are the most commonly encountered toxic substances that increase susceptibility to various diseases after prolonged exposure. We have previously shown that healthy volunteers living near a mining area had significant contamination with heavy metals associated with significant changes in the expression of some detoxifying genes, xenobiotic metabolizing enzymes, and DNA repair genes. However, alterations of most of the molecular target genes associated with diseases are still unknown. Thus, the aims of this study were to (a) evaluate the gene expression profile and (b) identify the toxicities and potentially relevant human disease outcomes associated with long-term human exposure to environmental heavy metals in mining area using microarray analysis. For this purpose, 40 healthy male volunteers who were residents of a heavy metal-polluted area (Mahd Al-Dhahab city, Saudi Arabia) and 20 healthy male volunteers who were residents of a non-heavy metal-polluted area were included in the study. Total RNA was isolated from whole blood using PAXgene Blood RNA tubes and then reversed transcribed and hybridized to the gene array using the Affymetrix U219 GeneChip. Microarray analysis showed about 2129 genes were identified and differentially altered, among which a shared set of 425 genes was differentially expressed in the heavy metal-exposed groups. Ingenuity pathway analysis revealed that the most altered gene-regulated diseases in heavy metal-exposed groups included hematological and developmental disorders and mostly renal and urological diseases. Quantitative real-time polymerase chain reaction closely matched the microarray data for some genes tested. Importantly, changes in gene-related diseases were attributed to alterations in the genes encoded for protein synthesis. Renal and urological diseases were the diseases that were most frequently associated with the heavy metal-exposed group. Therefore, there is a need for further studies to validate these genes, which could be used as early biomarkers to prevent renal injury.
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: hkorashy@ksu.edu.sa.
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Korashy
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Ibraheem M
authors.initials: IM
authors.lastname: Attafi
authors.affiliation: Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada.
authors.forename: Konrad S
authors.initials: KS
authors.lastname: Famulski
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Bakheet
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Hafez
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulaziz M S
authors.initials: AMS
authors.lastname: Alsaad
authors.affiliation: Central Laboratory, Research Center, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Abdul Rahman M
authors.initials: ARM
authors.lastname: Al-Ghadeer
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D004787:Environmental Pollution / Q000706:statistics & numerical data*; D020869:Gene Expression Profiling; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007668:Kidney / Q000378:metabolism; D008297:Male; D019216:Metals, Heavy / Q000378:metabolism / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D060888:Real-Time Polymerase Chain Reaction; D012529:Saudi Arabia; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D019216:Metals, Heavy
keywords: Heavy metals; Lead; Mercury; Microarray; Mining activity; Renal diseases