PMID- 15703262 OWN - NLM STAT- MEDLINE DCOM- 20050801 LR - 20161124 IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 85 IP - 1 DP - 2005 May TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces organ- specific differential gene expression in male Japanese medaka (Oryzias latipes). PG - 572-84 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant with well-known adverse effects in fish. In this study, we initially exploited suppression subtractive hybridization (SSH) as a screening tool to assess qualitative gene expression changes in whole brain, liver, and testis of adult male Japanese medaka (Oryzias latipes) exposed for 48 h to a single intraperitoneal-injected dose of TCDD (10 microg TCDD/kg body weight). Across these three organs, SSH identified a total of 335 unique genes. Each set of forward- and reverse-subtracted organ cDNA libraries consisted of a distinct gene list and corresponding distribution of biological processes, suggesting that transcript profiles of these libraries were highly organ-specific. Based on sequence match significance and frequencies within each set of organ libraries, genes hypothesized to be strongly responsive (42 total) within male medaka brain, liver, or testis were semi-quantitatively screened with replicate cDNA nylon membrane arrays. In addition, TCDD-treated male medaka were surveyed for gross histological analysis of brain, liver, and testis. In general, adverse histopathological changes were not observed in the brain, and glycogen depletion was observed only in the liver. However, significant histological changes occurred in the testis, and included disorganization of spermatogenesis at the testis periphery, disruption of the interstitium, Leydig cell swelling, and Sertoli cell vacuolation. Of the 42 genes screened by cDNA array analysis, cytochrome P450 1A (CYP1A) mRNA was the only transcript significantly higher in TCDD-exposed brain, whereas 12 transcripts (including CYP1A) were significantly higher in TCDD-exposed liver, and 34 transcripts were significantly lower in TCDD-exposed testis. Therefore, the degree of TCDD-induced alterations observed in each organ at a gross histological level corresponded well with the number and ontology of gene transcripts affected on the array. Based on real-time reverse transcription polymerase chain reaction (RT-PCR), relative CYP1A (but not AHR1) transcript levels were confirmed to be significantly higher in TCDD-treated brain and liver. However, CYP1A was not significantly induced in TCDD-exposed testis, suggesting that gene expression and histopathological responses observed in the testis at 48 h may be CYP1A-independent. Based on these data, unique liver-specific and testis-specific mRNA-level targets in male medaka were identified as promising biomarkers of acute TCDD-induced toxicity. FAU - Volz, David C AU - Volz DC AD - Integrated Toxicology Program and Nicholas School of the Environment and Earth Sciences, Duke University, Durham, North Carolina 27708-0328, USA. FAU - Bencic, David C AU - Bencic DC FAU - Hinton, David E AU - Hinton DE FAU - Law, J McHugh AU - Law JM FAU - Kullman, Seth W AU - Kullman SW LA - eng GR - 1R01 RR 018583/RR/NCRR NIH HHS/United States GR - 5P42 ES0004699/ES/NIEHS NIH HHS/United States GR - P30 ES03828/ES/NIEHS NIH HHS/United States GR - T32 ES07031/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050209 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Environmental Pollutants) RN - 0 (Polychlorinated Dibenzodioxins) SB - IM MH - Animals MH - Brain/drug effects/metabolism/pathology MH - Environmental Pollutants/*toxicity MH - Gene Expression/*drug effects MH - Gene Expression Profiling MH - Injections, Intraperitoneal MH - Liver/*drug effects/metabolism/pathology MH - Male MH - Oligonucleotide Array Sequence Analysis MH - Organ Specificity MH - Oryzias/*genetics MH - Polychlorinated Dibenzodioxins/*toxicity MH - Reverse Transcriptase Polymerase Chain Reaction MH - Testis/*drug effects/metabolism/pathology EDAT- 2005/02/11 09:00 MHDA- 2005/08/02 09:00 CRDT- 2005/02/11 09:00 PHST- 2005/02/11 09:00 [pubmed] PHST- 2005/08/02 09:00 [medline] PHST- 2005/02/11 09:00 [entrez] AID - kfi109 [pii] AID - 10.1093/toxsci/kfi109 [doi] PST - ppublish SO - Toxicol Sci. 2005 May;85(1):572-84. doi: 10.1093/toxsci/kfi109. Epub 2005 Feb 9.