T. Liu et al., Application of cDNA microarray to the study of arsenic-induced liver diseases in the population of Guizhou, China, TOXICOL SCI, 59(1), 2001, pp. 185-192
Arsenic is an environmental toxicant and a human carcinogen. Epidemiology s
tudies link human arsenic exposure to various diseases and cancers, includi
ng liver diseases and hepatocellular carcinoma. However, the molecular mech
anisms for arsenic toxicity and carcinogenicity are poorly understood. To b
etter understand these mechanisms, we used the human cancer cDNA expression
array to profile aberrant gene expression in arsenic-exposed populations i
n Guizhou, China. The selected patients had a history of exposure to enviro
nmental arsenic for at least 6-10 years, and had arsenic-induced skin lesio
ns and hepatomegaly. Samples were obtained by liver needle biopsy. Histolog
y showed degenerative liver lesions, such as chronic inflammation, vacuolat
ion, and focal necrosis. The University of North Carolina Hospitals provide
d normal human liver tissues from surgical resection or rejected transplant
s, Microarray was performed with total RNA from liver samples, and signal i
ntensities were analyzed with AtlasImage software and normalized with 9 hou
sekeeping genes. Means and SEM were calculated for statistical analysis. Ap
proximately 60 genes (10%) were differentially expressed in arsenic-exposed
human livers compared to controls. The differentially expressed genes incl
uded those involved in cell-cycle regulation, apoptosis, DNA damage respons
e, and intermediate filaments. The observed gene alterations appear to be r
eflective of hepatic degenerative lesions seen in the arsenic-exposed patie
nts. This array analysis revealed important patterns of aberrant gene expre
ssion occurring with arsenic exposure in human livers. Aberrant expressions
of several genes were consistent with the results of array analysis of chr
onic arsenic-exposed mouse livers and chronic arsenic-transformed rat liver
cells. Clearly, a variety of gene expression changes may play an integral
role in arsenic hepatotoxicity and possibly carcinogenesis.