Distribution of oval cells and c-myc mRNA expression in mouse hepatocarcinogenesis.
BACKGROUND
This study was designed to assess the roles of oval cells and c-myc mRNA in the process of hepatocarcinogenesis and to clarify the function of carcinogene c-myc in the development of hepatocellular carcinoma (HCC) and the mechanism of inhibitory function of uscharidin on HCC in mouse hepatocarcinogenesis.


METHODS
A total of 120 clean SD mice were divided into normal group, cancer induction group, and intervention group. The normal group was fed with standard forage while the rest two groups were given p-dimethylaminoazobenzene (DAB) to induce cancer. Thirteen weeks after induction of cancer, the two groups were fed with standard forage and water. Once the pattern was set up, the intervention group was given uscharidin injection into the abdominal cavity from the first week to the 14th week. On the 2nd, 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd, and 24th week, all mice were killed and biopsied from the liver lobe for pathological analysis. At the same time, the number of tumor nodes was counted and the expression of c-myc mRNA was tested by RT-PCR.


RESULTS
Since the 2nd week after cancer induction, proliferated oval cells could be seen in the portal area. Initially, the oval cells appeared in the cortical layer of the portal area, then proliferated gradually and immigrated into the liver parenchyma. In the period of fibrosis after liver proliferation, proliferated heaps of oval cells were noted in both portal and peripheral areas. In the period of carcinomatous change, oval cells could be seen both outside and inside of cancer nodes, but most of them were distributed outside. The c-myc gene was expressed negatively in the liver tissue of mice. The quantity of the expression began to increase at the time of infection of the liver and tended to increase with the degree of hepatic injury. In the period of canceration, the expression level of c-myc mRNA increased gradually. The intervention of uscharidin could not inhibit but delay the increase of the expression of c-myc mRNA.


CONCLUSIONS
Oval cells are closely related to hepatocarcinoma cells, which play an important role in the occurrence and development of hepatocarcinogenesis. Uscharidin can inhibit the occurrence of hepatocarcinogenesis or local spreading at the early stage of cancer induction by DAB, but it cannot inhibit the expression of c-myc.
Department of Hepatobiliary Surgery, Zhujiang Hospital of the First Military Medical University, Guangzhou 510282, China. fch58520@sina.com
Chi-Hua
CH
Fang
Gang-Qing
GQ
Zhang
Xin-Yong
XY
Zhu
Jia-Qing
JQ
Gong
D000818:Animals; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000473:pathology / Q000502:physiology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014361:Trypsin Inhibitors / Q000494:pharmacology; D004124:p-Dimethylaminoazobenzene
D002273:Carcinogens; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D004124:p-Dimethylaminoazobenzene