Echographic detection of diethylnitrosamine-induced liver tumors in rats and the effect of the intratumoral injection of an inhibitor of c-Jun N-terminal kinase.
OBJECTIVE
There have so far been few reports describing echographic studies of chemically-induced carcinogenesis in rodent livers. Using echography, we observed diethylnitrosamine-induced liver tumors in rats and examined the effect of an intratumoral injection of an inhibitor of c-Jun N-terminal kinase.


METHODS
Male Wistar rats were given 100 ppm of diethylnitrosamine for 6 weeks and their liver nodules were examined by echography weekly. The size of the nodules was measured and they were examined histologically. The effect of SP600125, an inhibitor of c-Jun N-terminal kinase, on the growth of rat hepatoma cell line McA-RH7777 was tested in vitro. Thereafter, SP600125 was injected into the liver nodules under echographic guidance in vivo and the changes in the proliferating cell nuclear antigen expression and size of the nodules were examined.


RESULTS
The four distinct lobes of rat livers were clearly observed by transabdominal echography. The nodules in the livers were first detected 6 weeks after the treatment began, when they were as small as 1.6 mm in diameter. The nodules thereafter became more malignant histologically as they grew larger than 4 mm. SP600125 decreased the expression of proliferating cell nuclear antigen and the growth of McA-RH7777 cells. After SP600125 was injected in vivo, the proliferating cell nuclear antigen level and the growth rate of the rat liver nodules all significantly decreased.


CONCLUSIONS
Our results indicate that echography is quite useful for follow-up studies of liver carcinogenesis in rats, and c-Jun N-terminal kinase might be another therapeutic target in liver neoplasms.
Hanajiri
Kazuyuki
K
Department of Gastroenterology, University of Tokyo, Tokyo, Japan.
Mitsui
Hiroshi
H
Maruyama
Toshiyuki
T
Hashimoto
Naoaki
N
Sata
Masataka
M
Omata
Masao
M
D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D015552:Injections, Intralesional; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014463:Ultrasonography
D000873:Anthracenes; D000970:Antineoplastic Agents; D018809:Proliferating Cell Nuclear Antigen; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D004052:Diethylnitrosamine; D048031:JNK Mitogen-Activated Protein Kinases