Genomic and proteomic profiling of responses to toxic metals in human lung cells.
Examining global effects of toxic metals on gene expression can be useful for elucidating patterns of biological response, discovering underlying mechanisms of toxicity, and identifying candidate metal-specific genetic markers of exposure and response. Using a 1,200 gene nylon array, we examined changes in gene expression following low-dose, acute exposures of cadmium, chromium, arsenic, nickel, or mitomycin C (MMC) in BEAS-2B human bronchial epithelial cells. Total RNA was isolated from cells exposed to 3  M Cd(II) (as cadmium chloride), 10  M Cr(VI) (as sodium dichromate), 3  g/cm2 Ni(II) (as nickel subsulfide), 5  M or 50  M As(III) (as sodium arsenite), or 1  M MMC for 4 hr. Expression changes were verified at the protein level for several genes. Only a small subset of genes was differentially expressed in response to each agent: Cd, Cr, Ni, As (5  M), As (50  M), and MMC each differentially altered the expression of 25, 44, 31, 110, 65, and 16 individual genes, respectively. Few genes were commonly expressed among the various treatments. Only one gene was altered in response to all four metals (hsp90), and no gene overlapped among all five treatments. We also compared low-dose (5  M, noncytotoxic) and high-dose (50  M, cytotoxic) arsenic treatments, which surprisingly, affected expression of almost completely nonoverlapping subsets of genes, suggesting a threshold switch from a survival-based biological response at low doses to a death response at high doses.
Andrew
Angeline S
AS
Department of Pharmacology and Toxicology, Dartmouth Medical School, Dartmouth College, 7927 Rubin Building, 452M-3, One Medical Center Drive, Lebanon, NH 03756-0001, USA. angeline.s.andrew@dartmouth.edu
Warren
Amy J
AJ
Barchowsky
Aaron
A
Temple
Kaili A
KA
Klei
Linda
L
Soucy
Nicole V
NV
O'Hara
Kimberley A
KA
Hamilton
Joshua W
JW
D018929:Cell Culture Techniques; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000473:pathology*; D019216:Metals, Heavy / Q000009:adverse effects*; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics
D019216:Metals, Heavy