Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive genes in mouse liver by serial analysis of gene expression.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic environmental pollutants that causes various biological effects on mammals. To identify the genes involved in hepatotoxicity and hepatocarcinogenesis induced by TCDD, we have conducted here serial analysis of gene expression of mouse liver 7 days after treatment with a single oral dose of 20 microg TCDD/kg body weight. We have sequenced total of 113,067 tags, including 56,420 tags and 56,647 tags from normal liver and TCDD-treated liver library, respectively. Statistical analysis showed that TCDD significantly altered 346 transcripts (p < 0.05) including 94 ESTs. The genes regulated by TCDD were not only the genes encoding drug metabolizing enzymes and stress response genes but also a wide variety of genes encoding cytoskeleton related proteins, signal transduction, and plasma proteins. This comprehensive gene expression analysis would provide novel genes that may help to clarify the mechanism of TCDD effects on mammalian liver, and also give a new approach for prevention and treatment.
Kurachi
Makoto
M
Department of Molecular Preventive Medicine & CREST, School of Medicine, University of Tokyo, Japan.
Hashimoto
Shin-ichi
S
Obata
Aya
A
Nagai
Shigenori
S
Nagahata
Tomoyuki
T
Inadera
Hidekuni
H
Sone
Hideko
H
Tohyama
Chiharu
C
Kaneko
Shuichi
S
Kobayashi
Ken-ichi
K
Matsushima
Kouji
K
D000818:Animals; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D016678:Genome; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger