Expression of inducible nitric oxide (NO) synthase but not prevention by its gene ablation of hepatocarcinogenesis with fibrosis caused by a choline-deficient, L-amino acid-defined diet in rats and mice.
Expression of inducible nitric oxide synthase (iNOS) and effects of iNOS gene ablation on the hepatocarcinogenesis associated with fibrosis caused by a choline-deficient, L-amino acid-defined (CDAA) diet, were examined in male F344 rats and C57BL/6J wild-type and iNOS-/- mice. Western blot, RT-PCR and immunohistochemical analyses revealed increased expression of iNOS protein and mRNA in the livers of rats and wild-type mice fed a CDAA diet for 12-80 weeks, associated with elevated serum NO(x) and liver nitrotyrosine levels. iNOS-/- mice demonstrated greater liver injury and fibrosis in the early stage than their wild-type counterparts, but this did not significantly affect the incidence and multiplicity of altered foci, adenomas and hepatocellular carcinomas in spite of immunohistochemical iNOS expression in these lesions. Results suggested no major determinant roles of the expressed iNOS in the development of liver tumors caused by the CDAA diet.
Denda
Ayumi
A
Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan. adenda@nmu-gw.cc.naramed-u.ac.jp <adenda@nmu-gw.cc.naramed-u.ac.jp>
Kitayama
Wakashi
W
Kishida
Hideki
H
Murata
Nao
N
Tamura
Kazutoshi
K
Kusuoka
Osamu
O
Tsutsumi
Masahiro
M
Nishikawa
Fumiko
F
Kita
Eiji
E
Nakae
Dai
D
Konishi
Yoichi
Y
Kuniyasu
Hiroki
H
D000818:Animals; D001483:Base Sequence; D002796:Choline Deficiency / Q000201:enzymology*; D017931:DNA Primers; D004032:Diet; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D052247:Nitric Oxide Synthase Type II