Identification of phenobarbitone‐modulated genes in mouse liver by differential display

Autor: Terry C. Orton, Claudia Garcia-Allan, Johanna M. Loughlin, James E. Sidaway, Peter G. Lord
Rok vydání: 1999
Předmět:
Zdroj: Journal of Biochemical and Molecular Toxicology. 14:65-72
ISSN: 1099-0461
1095-6670
Popis: The molecular basis of how rodent nongenotoxic hepatocarcinogens such as phenobarbitone cause liver-tumor formation is poorly understood. An early effect of phenobarbitone exposure is to induce hepatocyte proliferation transiently, and there is evidence that this may be important for subsequent tumor development. In this investigation, we have used the differential display reverse transcriptase polymerase chain reaction technique to analyze differential gene expression in male C57Bl/10J mouse liver during the mitogenic phase of the phenobarbitone response. Seventy-seven putative differentially expressed cDNAs were isolated by differential display, and 13 of them were subsequently confirmed as being differentially expressed (both increased and decreased by phenobarbitone). Seven of the cDNAs were homologous to known mouse or human genes (carboxylesterase, coagulation factor X, amine N-sulphotransferase, human protein disulphide isomerase-related protein, cytochrome c oxidase subunit IV, golgin-245, thioredoxin reductase, betaine-homocysteine methyl transferase) and the remainder were novel. The expression pattern of the sulphotransferase was further characterized, and in mouse liver it was found to be significantly induced by phenobarbitone and not by five other rodent nongenotoxic hepatocarcinogens. In summary, the technique has enabled the identification of previously uncharacterized genes whose expression patterns are differentially altered by phenobarbitone in the mouse liver. © 2000 John Wiley & Sons, Inc. J Biochem Toxicol 14: 65–72, 2000
Databáze: OpenAIRE