Carcinogenesis and Ito cell

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Administration of a choline deficient L-amino acid defined (CDAA) diet for 16 weeks led to the development of preneoplastic lesions that were positive for the placental form of glutathione S-transferase (GSTP) and induced hepatocellular carcinoma in 90% of rats after one year. Prolyl 4-hydroxylase inhibitor (HOE 077, 200 ppm) significantly reduced the size and incidence of preneoplastic lesions after 16 weeks and also the incidence of HCC (50%) in rats fed a CDAA diet for one year by the inactivation of Ito cell resulting in the prevention of fibrosis.Injection of pig serum into rats twice a week for 8 weeks induced.TGF-beta_1 mRNA expression and protein production resulting in liver fibrosis without parenchymal cell injury. Administration of a choline deficient L-amino acid defined (CDAA) diet for 6 weeks with or without pig serum pretreatment led to the development of preneoplastic lesions that were positive for the placental form of glutathione S- transferase (GSTP). Pig serum pretreatment induced more activated stellate cells with increased TGF-beta_1, mRNA expression and protein production in the livers of rats subsequently fed a CDAA diet for 6 weeks compared to rats fed the CDAA diet alone.These results indicate that pre-existing fibrosis with the activated stellate cells accelerates the development of preneoplastic lesions in a CDAA.diet model and that TGF-beta_1 induced by pig serum treatment failed to prevent the development of preneoplastic lesions in a CDAA-diet model.Cancer cell seems to prevent the activation of Ito cell in co-culture system but further examinations are necessary.