Gene expression signatures in peripheral blood cells from Japanese women exposed to environmental cadmium.
The objective of this study was to examine the effects of environmental cadmium (Cd) exposure on the gene expression profile of peripheral blood cells, using an original oligoDNA microarray. The study population consisted of 20 female residents in a Cd-polluted area (Cd-exposed group) and 20 female residents in a non-Cd-polluted area individually matched for age (control group). The mRNA levels in Cd-exposed subjects were compared with those in respective controls, using a microarray containing oligoDNA probes for 1867 genes. Median Cd concentrations in blood (3.55 microg/l) and urine (8.25 microg/g creatinine) from the Cd-exposed group were 2.4- and 1.9-times higher than those of the control group, respectively. Microarray analysis revealed that the Cd-exposed group significantly up-regulated 137 genes and down-regulated 80 genes, compared with the control group. The Ingenuity Pathway Analysis Application (IPA) revealed that differentially expressed genes were likely to modify oxidative stress and mitochondria-dependent apoptosis pathways. Among differentially expressed genes, the expression of five genes was positively correlated with Cd concentrations in blood or urine. Quantitative real-time PCR (RT-PCR) analysis validated the significant up-regulation of CASP9, TNFRSF1B, GPX3, HYOU1, SLC3A2, SLC19A1, SLC35A4 and ITGAL, and down-regulation of BCL2A1 and COX7B. After adjustment for differences in the background characteristics of the two groups, we finally identified seven Cd-responsive genes (CASP9, TNFRSF1B, GPX3, SLC3A2, ITGAL, BCL2A1, and COX7B), all of which constituted a network that controls oxidative stress response by IPA. These seven genes may be marker genes useful for the health risk assessment of chronic low level exposure to Cd.
Dakeshita
Satoru
S
Department of Preventive Medicine, Institute of Health Biosciences, the University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan.
Kawai
Tomoko
T
Uemura
Hirokazu
H
Hiyoshi
Mineyoshi
M
Oguma
Etsuko
E
Horiguchi
Hyogo
H
Kayama
Fujio
F
Aoshima
Keiko
K
Shirahama
Satoshi
S
Rokutan
Kazuhito
K
Arisawa
Kokichi
K
D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001773:Blood Cells / Q000187:drug effects*; D002104:Cadmium / Q000009:adverse effects* / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D016000:Cluster Analysis; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000097:blood / Q000652:urine; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D006801:Humans; D007564:Japan; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment
D004785:Environmental Pollutants; D005819:Genetic Markers; D012333:RNA, Messenger; D002104:Cadmium