title: Gene expression profiling in streptozotocin treated mouse liver using DNA microarray.
abstract: Streptozotocin (SZ) is known to exert toxic effects not only on pancreatic islet beta cells but also on other organs including liver. For analyzing changes in genes expression associated with SZ toxicity, we performed DNA microarray analyses on the liver obtained from SZ-treated mice. Eight-week-old male ICR mice were treated i.p. with 200 mg/kg of SZ, and the blood and liver were taken at 6, 24 and 48 h after the treatment. Labeled cRNA prepared from total RNA of the liver was hybridized to the GeneChip Murine Genome U74A V.2 (Affymetrix). The number of the probe sets, which were clearly up-regulated or down-regulated, were over 100 at 6 and 24h after the SZ-treatment, and it decreased at 48 h after the treatment. Many of the up-regulated genes were categorized into cell cycle/apoptosis related genes, immune/allergy related genes and stress response/xenobiotic metabolism related genes. On the other hand, genes related to glucose, lipid and protein metabolisms were down-regulated. These changes started prior to the elevation of the serum glucose levels, indicating the direct action of SZ on the liver rather than the secondary effect of diabetes. This may be related with the previously reported hepatic changes such as lipid peroxidation, mitochondrial swelling and inhibition of hepatocyte proliferation observed before the development of hyperglycemia.
authors.affiliation: Exploratory Toxicology and DMPK Research Laboratory, Tanabe Seiyaku Co Ltd, 2-2-50, Kawagishi, Toda, Saitama 335, Japan. e-kume@tanabe.co.jp
authors.forename: Eisuke
authors.initials: E
authors.lastname: Kume
authors.forename: Chinami
authors.initials: C
authors.lastname: Aruga
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ishizuka
authors.forename: Kaori
authors.initials: K
authors.lastname: Takahashi
authors.forename: Satoko
authors.initials: S
authors.lastname: Miwa
authors.forename: Masahito
authors.initials: M
authors.lastname: Itoh
authors.forename: Hisako
authors.initials: H
authors.lastname: Fujimura
authors.forename: Wataru
authors.initials: W
authors.lastname: Toriumi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kitamura
authors.forename: Kunio
authors.initials: K
authors.lastname: Doi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013311:Streptozocin / Q000633:toxicity*
chemical_list: D000903:Antibiotics, Antineoplastic; D013311:Streptozocin