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KMID : 0379520050210030209
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한국독성학회지
2005 Volume.21 No. 3 p.209 ~ p.218
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Effects of Recombinant Human Erythropoietin Treatment in Male Cynomolgus (Macaca fascicularis) Monkeys (II): Gene Expression Profiling in Spleen
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Yoon Seok-Joo
Hwang Ji-Yoon
Lim Jung-Sun
Jung Sun-Young
Kim Yong-Bum
Kim Dal-Hyun
Kwon Myung-Sang
Han Sang-Seop
Kim Choong-Yong
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Abstract
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We investigated effects of recombinant human erythropoietin (rHuEPO) on profiles of mRNA transcripts in 6 male cynomolgus (M. fascicularis) monkey’’s spleen for 4 weeks. Six monkeys, composed of control and treatment group (Control : M1, M2, M3: Treatment : M4, M5, M6) were intravenously administered 3 times per week without or with a dose of rHuEPO 2730 IU/0.1 ml/kg. After 4 weeks rHuEPO treatment, spleen was removed for RNA isolation. Splenic gene expression was assessed using Affymetrix U133A 2.0 arrays containing 18,400 transcripts and variants, including 14,500 well-characterized human genes. Gene expression pattern was very different between individuals even in same treatment. In rHuEPO treated groups showed number of genes were up- or down-regulated (M4: 79: M5: 48; M6: 73 genes). Six genes (epidermal growth factor receptor, calgranulin A, estrogen receptor binding site associated antigen, matrix metalloproteinase 19, zinc finger and BTB domain containing 16, progestin and adipoQ receptor) were commonly expressed in rHuEPO treated group. The different individual response could be major considering factor in monkey experiment. Further study is needed to clarify the different individual response to rHuEPO in molecular level. This study will be valuable in the fundamental understanding and validation of molecular toxicology for bio-generic drugs including rHuEPO in cynomolgus monkey.
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KEYWORD
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rHuEPO, Cynomolgus monkey, Gene expression, Spleen, Microarray
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