Identification of genes that are induced after cadmium exposure by suppression subtractive hybridization.
The heavy metal cadmium is a xenobiotic toxicant of environmental and occupational concern and it has been classified as a human carcinogen. Inhalation of cadmium has been implicated in the development of emphysema and pulmonary fibrosis, but, the detailed mechanism by which cadmium induces adverse biological effects is not yet known. Therefore, we undertook the investigation of genes that are induced after cadmium exposure to illustrate the mechanism of cadmium toxicity. For this purpose, we employed the polymerase chain reaction (PCR)-based suppression subtractive hybridization (SSH) technique. We identified 29 different cadmium-inducible genes in human peripheral blood mononuclear cells (PBMCs), such as macrophage migration inhibitory factor (MIF), lysophosphatidic acid acyltransferase-alpha, enolase-1alpha, VEGF, Bax, and neuron-derived orphan receptor-1 (Nor-1), which are known to be associated with inflammation, cell survival, and apoptosis. Induction of these genes by cadmium treatment was further confirmed by semi-quantitative reverse-transcription PCR. Further, we found that these genes were also induced after cadmium exposure in normal human lung fibroblast cell line, WI-38, suggesting potential use of this induction profile to monitor cadmium toxicity in the lung.
Shin
Hye-Jin
HJ
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Kwangjin-gu, 140-747, Seoul, South Korea. molee@sejong.ac.kr
Park
Kun-Koo
KK
Lee
Byeong-Hoon
BH
Moon
Chang-Kyu
CK
Lee
Mi-Ock
MO
D000217:Acyltransferases / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008222:Lymphokines / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D009693:Nucleic Acid Hybridization; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008263:Macrophage Migration-Inhibitory Factors; C490412:NR4A3 protein, human; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051028:bcl-2-Associated X Protein; D002104:Cadmium; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; D010751:Phosphopyruvate Hydratase