Furan Induced Characteristic Glutathione S-Transferase Placental Form-Positive Foci in Terms of Cell Kinetics and Gene Expression. (August 2020)

• Record Type: Journal Article
• Authors: Takasu, Shinji; Ishii, Yuji; Kijima, Aki; Ogawa, Kumiko; Nakane, Sae; Umemura, Takashi
• Is Part Of: Toxicologic pathology. Volume 48:Number 6(2020)
• Page Start: 756
• Page End: 765
• Publication Date: 2020-08
• Subjects: SOX9 -- glutathione S-transferase placental form-positive foci -- hepatocarcinogen; Pathology -- Periodicals; Toxicology -- Periodicals; Pathology; Toxicology; 615.9
• DOI: 10.1177/0192623320948782
• Languages: English
• ISSNs: 0192-6233

Abstract

Glutathione S -transferase placental form-positive (GST-P + ) foci are markers of preneoplastic lesions in rat hepatocarcinogenesis. Our previous studies using reporter gene transgenic rats showed that furan, a hepatocarcinogen in rodents, rapidly induces the formation of GST-P + foci after short exposure without reporter gene mutation. We hypothesized that GST-P + foci induced by furan may have biological characteristics different from those induced by diethylnitrosamine (DEN), a genotoxic hepatocarcinogen. Accordingly, we compared the cell kinetics of GST-P + foci after cessation of DEN treatment and performed comprehensive gene expression in DEN- or furan-induced GST-P + foci. The number and area of DEN-induced GST-P + foci were increased after cessation of treatment, whereas furan decreased these parameters. Size distribution analysis showed that large furan-induced GST-P + foci disappeared after cessation of treatment. Hierarchical cluster analysis showed that all samples from GST-P + foci induced by furan were separated from those induced by DEN. SOX9 expression was upregulated in furan-induced GST-P + foci and was detected by immunohistochemistry in large furan-induced GST-P + foci. Our results indicated that large furan-induced GST-P + foci were quite different from DEN-induced GST-P + foci at the molecular and cellular levels. And one of the properties of disappearing large GST-P + foci were characterized by inclusion of hepatocytes expressing SOX9.