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.

Nitric oxide production by primary liver cells isolated from amino acid diet-fed rats.

Primary mixed liver cells were isolated from rats that had been fed an amino acid (AA) diet in which natural protein was replaced with a defined mixture of pure AAs. Nitric oxide (NO) production from these cells in vitro was monitored using a nitric oxide (NO)-selective fluorescent probe, diaminofluorescein, followed by flow cytometric analysis. High levels of NO fluorescence were seen in approximately half of liver cells isolated from rats fed an AA diet for 1-7 days, whereas there was baseline fluorescence in cells obtained from regular diet-fed rats.

Inhibition of the development of hepatocellular carcinomas by phenyl N-tert-butyl nitrone in rats fed with a choline-deficient, L-amino acid-defined diet.

Effects of phenyl N-tert-butyl nitrone (PBN), a spin-trapping agent, on the development of frank cancers were examined in male Wistar rats fed with a choline-deficient, l-amino acid-defined (CDAA) diet for 70 weeks. PBN (0.065% in the drinking water) reduced incidences, multiplicities and possibly sizes of both hepatocellular adenomas and carcinomas when administered for all 70 weeks or only for the first 26 weeks, and those of carcinomas but not adenomas, when administered only for the last 44 weeks.

Effects of phenyl N-tert-butyl nitrone and its derivatives on the early phase of hepatocarcinogenesis in rats fed a choline-deficient, L-amino acid-defined diet.

The present study examined the effects of various derivatives of a radical trapping agent, phenyl N-tert-butyl nitrone, on the early phase of hepatocarcinogenesis in male Wistar rats fed a choline-deficient, L-amino acid-defined diet for 16 weeks. The derivatives used were 4-hydroxyphenyl (a physiologically major metabolite), 3-hydroxyphenyl, 2-hydroxyphenyl and 2-sulfoxyphenyl N-tert-butyl nitrone, and their effects were studied in a comparison with those of the parent compound, phenyl N-tert-butyl nitrone. The sizes of putatively preneoplastic, glutathione S-transferase placental form-positive lesions and the levels of extra-nuclear oxidative injury of hepatocytes, using the formation of 2-thiobarbituric acid-reacting substances as a parameter, were decreased by all doses (0.

Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S-transferase placental form positive foci: a possible reactive oxygen species mechanism.

Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals, which are epidemiologically significant chemicals in relation to liver cancer in mammals. The present study was conducted to determine the promoting effects of organic arsenicals related to DMA [monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO)] on rat liver carcinogenesis using a liver medium-term bioassay (the Ito test). Male, 10-week-old, F344 rats were given a single i.

Inhibitory effects of lemon grass (Cymbopogon citratus, Stapf) extract on the early phase of hepatocarcinogenesis after initiation with diethylnitrosamine in male Fischer 344 rats.

Effects of lemon grass extract (LGE) on hepatocarcinogenesis were examined in male Fischer 344 rats, administered diethylnitrosamine (DEN) at three weekly intraperitoneal doses of 100 mg/kg body weight and partially hepatectomized at the end of week 5. LGE was given at dietary concentrations of 0, 0.2, 0.

Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide.

Expression of cyclooxygenase (COX)-2 protein during rat hepatocarcinogenesis associated with fatty change, fibrosis, cirrhosis and oxidative DNA damage, caused by a choline-deficient, L-amino acid-defined (CDAA) diet were investigated in F344 male rats, along with the chemopreventive efficacy of the specific COX-2 inhibitor, nimesulide (NIM). Nimesulide, which was administered in the diet at concentrations of 200, 400, 600 and 800 p.p.

Development of hepatocellular adenomas and carcinomas associated with fibrosis in C57BL/6J male mice given a choline-deficient, L-amino acid-defined diet.

Development of hepatocellular carcinomas in rats caused by a choline-deficient, L-amino acid-defined (CDAA) diet, usually associated with fatty liver, fibrosis, cirrhosis and oxidative DNA damage, has been recognized as a useful model of hepatocarcinogenesis caused by endogenous factors. In the present study, in order to further explore involved factors and genes, we established an equivalent model in spontaneous liver tumor-resistant C57BL/6J mice. Six-week-old males and females were continuously fed the CDAA diet and histological liver lesions and oxidative DNA damage due to 8-hydroxydeoxyguanosine (8-OHdG) were examined after 22, 65 and 84 weeks.

Lack of promoting effect due to oral administration of dimethylarsinic acid on rat lung carcinogenesis initiated with N-bis(2-hydroxypropyl)nitrosamine.

Dimethylarsinic acid (DMA), a major metabolite of inorganic arsenics, and arsenic exposure is associated with tumor development in a wide variety of human tissues. In the present study, we examined whether DMA has tumor-promoting activity on rat lung carcinogenesis initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male, 8-week-old, F344 rats were treated with DHPN at a concentration of 0.