Differential expression of genes during aflatoxin B1-induced hepatocarcinogenesis in tree shrews

AIM:Through exploring the regulation of gene expressionduring hepatocarcinogenesis induced by aflatoxin B1(AFB1),to find out the responsible genes for hepatocellular carcinoma(HCC) and to further understand the underlying molecularmechanism.METHODS:Tree shrews (Tupaia belangerichinensis)weretreated with or without AFB1for about 90 weeks.Liverbiopsies were performed regularly during the animalexperiment.Eight shares of total RNA were respectivelyisolated from 2 HCC tissues,2 HCC-surrounding non-cancerous liver tissues,2 biopsied tissues at the early stage(30th week) of the experiment from the same animals asabove,1 mixed sample of three liver tissues biopsied at thebeginning (0th week) of the experiment,and another 1 mixedsample of two liver tissues from the untreated control animalsbiopsied at the 90th week of the experiment.The sampleswere then tested with the method of AtlasTMcDNA microarrayassay.The levels of gene expression in these tissues takenat different time points during hepatocarcinogenesis werecompared.RESULTS:The profiles of differently expressed genes werequite different in different ways of comparison.At the sameperiod of hepatocarcinogenesis,the genes in the samefunction group usually had the same tendency for up-ordown-regulation.Among the checked 588 genes that wereknown to be related to human cancer,89 genes (15.1%)were recognized as“important genes”because they showedfrequent changes in different ways of comparison.Thedifferentially expressed genes during hepatocarcinogenesiscould be classified into four categories:genes up-regulatedin HCC tissue,genes with similar expressing levels in bothHCC and HCC-surrounding liver tissues which were higherthan that in the tissues prior to the development of HCC, genes down-regulated in HCC tissue,and genes up-regulatedprior to the development of HCC but down-regulated afterthe development of HCC.CONCLUSION:A considerable number of genes couldchange their expressing levels both in HCC and in HCC-surrounding non-cancerous liver tissues.A few modulargenes were up-regulated only in HCC but not in surroundingliver tissues,while some apoptosis-related genes weredown-regulated in HCC and up-regulated in surroundingliver tissues.To compare gene-expressing levels amongthe liver tissues taken at different time points duringhepatocarcinogenesis may be helpful to locate theresponsible gene (s) and understand the mechanism forAFB1induced liver cancer.