title: A toxicogenomic approach for identifying biomarkers for myelosuppressive anemia in rats.
abstract: Myelosuppressive anemia is a serious side effect associated with several drugs. Thus, there is an increasing demand for sensitive biomarkers for the early detection of myelosuppressive anemia during toxicological studies. We applied a toxicogenomic approach to identify useful biomarker genes reflecting myelosuppressive anemia in the rat liver. Expression of the hemoglobin beta chain complex (Hbb), aminolevulinic acid synthase 2 (Alas2), and cell division cycle 25 homolog B (Cdc25b) genes changed as a result of anemia induced by the myelosuppressive agents linezolid, cisplatin, and carboplatin, suggesting that these genes may be suitable biomarkers. Moreover, evaluation of perfused and unperfused livers indicated that changes in the expression of these genes originate in circulating reticulocytes in the liver. Erythroid differentiation-associated changes in expression of the Hbb, Alas2, and Cdc25b genes were confirmed in vitro using Friend leukemia cells. In conclusion, our current research provides novel evidence that gene expression in circulating reticulocytes contained in the liver changes dramatically under myelosuppressive conditions. While further large-scale validation studies are needed, our results indicate that the genes we identified might be useful biomarkers for the sensitive detection of myelosuppressive anemia in rats.
authors.affiliation: Drug Developmental Research Laboratories, Shionogi & Co. Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan. takeki.uehara@shionogi.co.jp
authors.forename: Takeki
authors.initials: T
authors.lastname: Uehara
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kondo
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
authors.forename: Mikinori
authors.initials: M
authors.lastname: Torii
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D020869:Gene Expression Profiling; D005819:Genetic Markers; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043922:Toxicogenetics
chemical_list: D005819:Genetic Markers