Ultrasonographic evidence of phenotypic instability during hepatocarcinogenesis in N-nitrosomorpholine-treated rats.
Carcinogen-induced hepatoma in immunocompetent animal models has shown a progress similar to the clinical course of human hepatoma. Ultrasonography (US) was used for consecutive evaluation of the phenotypic changes in Sprague-Dawley rats exposed for 8 weeks to N-nitrosomorpholine (NNM, 200 mg/L). Three distinctive US findings were ascites, coarseness (defined as small and heterogeneously widespread increased echogenecity), and nodularity (defined as a >0.6-cm-sized echogenic region and clearly showing a tumor-like mass). Abdominal ascites was observed in 5 of 26 rats at week 8 NNM posttreatment and the number of rats showing ascites gradually increased. Coarseness (22 of 26 rats) and nodularity (1 of 18) appeared at weeks 8 and 17 NNM posttreatment, respectively. The gross and histological findings indicated that coarseness and nodularity shown in US reflected fibrosis and hepatocellular carcinoma or cholangiofibroma, respectively. The computer-aided quantification of coarseness and nodularity showed that the regression-linked phenotypic instability was present in coarseness but not in nodularity. We conclude that the heterogeneity of preneoplasia in NNM-treated rats might be induced by phenotypic instability rather than random initiating events of preneoplastic lesion.
Institute of Medical Science, Department of Radiology, Medical College of Dong-A University, Busan 602-714, South Korea.
Jong-Young
JY
Oh
Jin-Sook
JS
Jeong
Yu-jin
YJ
Kim
Kyoung-Jin
KJ
Nam
Byung-Ho
BH
Park
Eun-Young
EY
Kwon
Young-Hoon
YH
Kim
Tae-Ho
TH
Hwang
D000818:Animals; D001201:Ascites / Q000150:complications / Q000000981:diagnostic imaging; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000150:complications / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000139:chemically induced / Q000150:complications / Q000000981:diagnostic imaging; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000150:complications / Q000000981:diagnostic imaging*; D008297:Male; D009602:Nitrosamines; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
D009602:Nitrosamines; C002741:N-nitrosomorpholine