Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the copper concentrations in the non-cancerous and cancerous liver tissues of LEC rats with hereditary hepatitis and spontaneous hepatoma by atomic absorption spectrophotometry. Copper concentration in the non-cancerous livers of 29-month-old male LEC rats was comparable to that in the livers of LEC rats aged 2, 3 and 8 months whose hepatic copper concentrations were more than 40 times those of normal LEA rats. Copper concentration in spontaneously developed hepatocellular carcinomas of the 29-month-old male LEC rats was lower than that in the surrounding non-cancerous liver tissues, but was still more than 39 times that of 8-month-old male LEA rats. These findings suggest that in LEC rats an abnormal copper metabolism may be maintained during the process of hepatic carcinogenesis.
 ...
PMID:Abnormal copper accumulation in non-cancerous and cancerous liver tissues of LEC rats developing hereditary hepatitis and spontaneous hepatoma. 190 94

The LEC rat is a mutant inbred strain isolated from Long-Evans rats, which spontaneously develops hepatitis and hepatoma with high frequency. In this study, copper profiles of LEC rats, including copper concentration in the liver and concentrations of copper and ceruloplasmin in the serum, were investigated. It was found that copper accumulated in the liver of LEC rats immediately prior to the onset of hepatitis with a concentration of more than 50 times that of normal LEA rats, and serum concentrations of copper and ceruloplasmin decreased markedly, which resembled biochemically characteristic features of human Wilson's disease. Administration of d-penicillamine (100 mg/Kg/day p. o), a chelating agent, reduced the hepatic copper level and completely inhibited the development of hepatitis in LEC rats. Copper also accumulated in both cancerous and non-cancerous liver tissues of three 29-month old male LEC rats which had spontaneously developed hepatocellular carcinomas. These findings suggest that the hepatitis in LEC rats is caused by copper toxicity, and that the abnormal copper metabolism may be involved in hepatic carcinogenesis in the LEC rats. Therefore, it is considered that the LEC rat will provide a promising animal model for not only elucidating the pathogenesis of Wilson's disease and developing treatment strategies of the disease, but also for studying the role of copper in hepatic carcinogenesis.
 ...
PMID:[Abnormal hepatic copper accumulation and its significance in LEC rats developing spontaneous hepatitis and hepatoma]. 195 41

1,2-Dimethylhydrazine-HCl (DMH-2HCl) is derived from the natural toxin cycasin, and is extensively used to induce cancers in experiments with rodents. We examined the toxicity of DMH-2HCl, incorporated into purified diets varying in protein, to determine concentrations compatible with long-term survival in B6C3H1 mice. Initial studies showed single-dose oral LD50 values (95% confidence intervals) of 26 (18-32) mg DMH-2HCl/kg body weight for males, and 60 (53-65) for females. A 6-wk study was performed with diets containing 10 or 40% soybean protein with doses of 0, 11.25, 22.5, 45, 90, and 180 mg DMH-2HCl/kg diet. All mice fed the highest dose were removed from the study due to severe toxicity. Declines in food consumption and body weight occurred in both sexes, accelerated with increasing log(DMH) dose, and were substantially more severe in groups fed 10% protein. A 5-mo study was subsequently performed with male mice fed 10 or 40% protein diets containing doses of 0, 15, 30, or 45 mg DMH-2HCl/kg diet. In this longer study, dose-related declines of food intake and body weight were also more pronounced with 10% protein. Histopathologic examination of samples from 29 organs/tissues revealed hepatic changes most commonly, and these were more severe at higher DMH levels. Lesions ranged from focal centrilobular hepatocellular necrosis to severe toxic hepatitis, associated with lobular disorganization and hepatocellular hypertrophy. Frequent dose-dependent lesions were also found in kidneys, adrenals, and heart. Renal changes included focal subcapsular fibrosis with atrophy, and hyperplasia of the tubular epithelium. Adrenal cortical hypertrophy was noted at the two highest DMH doses. Focal cardiac myocytolysis was also noted at high DMH doses. Renal damage occurred only rarely in the absence of liver pathology, and adrenal hypertrophy only rarely without renal damage. Cardiac myocytolysis was found in 14% of mice without hepatic, renal, or adrenal damage, but in 62% of those with lesions in each of those organs. No evidence of gastrointestinal toxicity was observed. Hepatic, renal, and adrenal lesions were more frequent and severe in mice fed the low-protein diet. The protective effect of high protein was DMH-dose dependent. The lower doses in these studies could be used to investigate effects of diet, cocarcinogens, or chemopreventative agents on carcinogenesis resulting from chronic, low-level dietary exposure to DMH.
 ...
PMID:Dietary protein and chronic toxicity of 1,2-dimethylhydrazine fed to mice. 201 52

The study of two major risk factors in the development of hepatocellular carcinoma, namely persistent hepatitis virus infection and exposure to dietary aflatoxins, has been hampered by lack of an experimental system. To this end we have used a Pekin duck model to examine the effect of congenital duck hepatitis B virus (DHBV) infection and aflatoxin B1 (AFB1) exposure in the induction and development of liver cancer. AFB1 was administered to DHBV infected or noninfected ducks at two doses (0.08 and 0.02 mg/kg) by i.p. injection once a week from the third month posthatch until they were sacrificed (2.3 years later). Two control groups of ducks not treated with AFB1 (one of which was infected with DHBV) were observed for the same period. Each experimental group included 13-16 ducks. Higher mortality was observed in ducks infected with DHBV and treated with AFB1 compared to noninfected ducks treated with AFB1 and other control ducks. In the groups of noninfected ducks treated with high and low doses of AFB1, liver tumors developed in 3 of 10 and 2 of 10 ducks; in infected ducks treated with the high dose 3 of 6 liver tumors were observed and none in the low dose of AFB1. No liver tumors were observed in the two control groups. Ducks infected with DHBV and treated with AFB1 showed more pronounced periportal inflammatory changes, fibrosis, and focal necrosis compared to other groups. All DHBV carrier ducks showed persistent viremia throughout the observation period. An increase of viral DNA titers in livers and sera of AFB1 treated animals compared to infected controls was frequently observed. No DHBV DNA integration into the host genome was observed, although in one hepatocellular carcinoma from an AFB1 treated duck, an accumulation of viral multimer DNA forms was detected. The metabolism of AFB1 in infected and noninfected duck liver was also examined. The study on the role of DHBV infection and AFB1 in the etiopathogenesis of liver tumors may help to clarify some of the basic mechanisms of carcinogenesis.
 ...
PMID:Contribution of aflatoxin B1 and hepatitis B virus infection in the induction of liver tumors in ducks. 210 70

It is reported that the number of hepatocellular carcinoma (HCC) in Japan is increasing and this is mainly due to the increase of HBsAg negative HCC patients with history of blood transfusion. However 80% of HCC patients are positive for HBV related serum markers. HBV DNA is detected by PCR method in 15% of HBsAg negative HCC patients with other HBV marker. These findings indicated that at least 40% of HCC patients in Japan are closely related to HBV infection. Several hypotheses on the mechanism of carcinogenesis by HBV have been proposed, however none of these has yet to be established. The type C hepatitis virus (HCV) reported by Chiron Co. is thought to be the majority of viruses which cause chronic non A non B hepatitis in Europe, United States and also Japan. The rate of anti-HCV in HBsAg negative HCC patients is about 70% in Japan. As strategies for HCC, the following 3 steps should be established; 1) prophylaxis against infection, 2) prevention of progression of liver cirrhosis, and 3) early detection of HCC. Though the role of hepatitis virus in hepatocarcinogenesis has not yet been established, it is thought that HBV and HCV are responsible for about 85% of HCC patients in terms of the development of liver cirrhosis which frequently associates with HCC. A marked decrease of HCC in Japan is forthcoming through the establishment of prophylaxis against HBV and HCV infection.
 ...
PMID:[Current status and therapeutic strategy for hepatocellular carcinoma]. 215 67

The existence of facultative stem cells in the liver has been advocated based on observations from models of carcinogenesis in rat liver. Observations of human liver material from cases of fulminant hepatitis have shown the presence of ductular hepatocytes expressing markers of both hepatocytes and bile duct cells. We describe the morphologic features and antigenic expression of a population of ductular hepatocytes identified in a patient with end-stage cirrhosis resulting from hepatitis B infection and secondary biliary cirrhosis. By conventional light microscopy and electron microscopy, ductular hepatocytes were seen to form pseudoductules within periportal areas. Using immunohistochemical methods, these ductular hepatocytes were found to be positive for both the hepatitis B surface antigen and bile duct epithelial cytokeratin, phenotypic markers classically restricted to expression on hepatocytes and bile duct epithelium, respectively. These findings show definitively that ductular hepatocytes are intermediate cells bearing morphologic and phenotypic characteristics of both hepatocytes and bile duct epithelium. The presence of these cells indicates the existence of facultative stem cells in the adult mammalian liver.
 ...
PMID:Characterization of ductular hepatocytes in end-stage cirrhosis. 232

The past decade has seen a dramatic increase in the number of approaches available for the study of hepadnavirus and hepatitis delta virus infections. In this review, we have summarized the recent applications of these approaches to the study of virus replication, tissue specificity, liver injury and hepatocellular carcinogenesis.
 ...
PMID:Experimental systems for the study of hepadnavirus and hepatitis delta virus infections. 264 12

Since the early 1960s, when aflatoxin, the mold-produced contaminant of a number of important food commodities, was found to be a potent hepatocarcinogen for laboratory rats, there has been a sustained search for evidence to support the regulatory presumption that aflatoxin is a probable human carcinogen. The developing laboratory evidence of differences between species in metabolism of aflatoxin and susceptibility to its oncogenic effects indicated that humans were probably refractory to aflatoxin carcinogenesis, but the early epidemiological evidence indicated otherwise. That epidemiological evidence, however, contained flaws so that Working Groups of the International Agency for Research on Cancer (IARC) meeting in 1970, 1976, and 1982, although ignoring the biochemical evidence, did consider the available epidemiological evidence insufficient for a conclusion of human carcinogenicity. During the 1970s and 1980s, studies on the connection between chronic infection with hepatitis B virus (HBV) and primary liver cell cancer (PLC), the expected lesion from aflatoxin exposure, had established a very strong etiological relationship between HBV and PLC. Since all the epidemiological studies of aflatoxin and PLC conducted prior to 1982 had been of populations with endemic HBV infection, and, in addition to other flaws, had not been controlled for this confounding factor, there was a solid basis for their rejection. Most epidemiological studies in the 1980s of aflatoxin and PLC were either in the United States, where HBV-infected groups could be excluded from the study, or, when in areas of chronic HBV infection, attempts were made to include that factor. The study of U.S. populations showed no difference in mortality rates from PLC that could be attributed to aflatoxin exposure. The studies of populations with endemic HBV infection produced no convincing evidence to support a primary role for aflatoxin in the induction of human PLC, although an accessory role to HBV infection for aflatoxin could not be ruled out. However, the epidemiological studies of the HBV/PLC relation indicate that an accessory factor is not an essential condition, a conclusion supported by animal models and a laboratory study that specifically found no interaction between aflatoxin and a hepatitis virus in the duck, a species in which liver cancer can be induced by either agent. It was surprising that an IARC Working Group meeting in 1987 concluded, on the basis of much of this evidence that was available at that time, and citing other studies that appear to be irrelevant to the issue, that there was sufficient evidence to consider aflatoxin a probable human carcinogen.
 ...
PMID:Aflatoxin is not a probably human carcinogen: the published evidence is sufficient. 269 Jan 97

The metabolism of chemical carcinogens was investigated in liver preparations from 28 captive woodchucks (Marmota monax). Of these, 23 were naturally infected with the woodchuck hepatitis virus (WHV), and eight also had primary hepatocellular carcinoma (PHC). Twenty-nine parameters were investigated in liver subcellular fractions, including cross-reactivity with HBsAg, and biochemical parameters, such as gamma-glutamyl transpeptidase, cytochrome P-450 and microsomal monooxygenases (aryl hydrocarbon hydroxylase, ethoxycoumarin and ethoxyresorufin deethylases, aminopyrine and dimethylnitrosamine demethylases, and testosterone 7 alpha-, 16 alpha- and 6 beta-hydroxylases), uridine 5'-diphosphoglucuronosyl transferase, GSH and related enzymes (peroxidase, reductase and S-transferase), as well as other cytosolic enzyme activities (glucose 6-phosphate and 6-phosphogluconate dehydrogenases, NADPH- and NADH-dependent diaphorases, and DT diaphorase). In addition, liver preparations were used in order to quantify the metabolic activation into bacterial mutagens of five procarcinogens (aflatoxin B1, the pyrolysis products Trp-P-2 and MeIQ, 2-aminofluorene and dimethylnitrosamine) and the decrease of potency of three direct-acting mutagens (sodium dichromate, ICR 191 and 4-nitroquinoline 1-oxide). WHV infection produced a significant stimulation of carcinogen metabolism, as shown by the simultaneous change in detoxification parameters (GSH depletion) and activation indices (enhancement of microsomal monooxygenases and of procarcinogen activation into mutagenic metabolites). There were no significant differences between WHV-positive samples from animals without PHC and the noncancerous tissue of PHC-bearing animals, whereas a decrease of both activation and detoxification indices was recorded in the tumorous tissue. There was a considerable interindividual variability among WHV carriers, which was tentatively ascribed to genetic factors. Pregnancy was the only known factor influencing the results in WHV carriers. However, even by excluding pregnant animals, the effects on carcinogen metabolism produced by WHV infection were still statistically significant. These results, together with previous data obtained in humans, revealed that metabolic factors may play a role in the synergism between viral hepatitis and chemical hepatocarcinogens in the etiopathogenesis of PHC.
Carcinogenesis 1989 Jun
PMID:Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus. 272 Sep 3

The Long-Evans rat with a cinnamon-like coat color (LEC rat) is a mutant strain displaying hereditary hepatitis with severe jaundice. The age related difference in microsomal dealkylation of pentoxyresorufin and ethoxyresorufin was examined. The enzyme activity levels of pentoxyresorufin O-depentylase in LEC rats were decreased to 25% of the levels in control [Long-Evans rats with an agouti coat color (LEA rats)]. In contrast, ethoxyresorufin O-deethylase exhibited a much less marked difference between the strains. In parallel with these strain differences in enzyme activities, a decrease in phenobarbital (PB) inducible P450 isozymes, mainly P450b and P450e, was observed by Western blot analysis. The level of P450PB in LEC rats was more markedly depressed than in the LEA strain. On the other hand, microsomes from uninduced LEC rat liver had more 3-methylcholanthrene (MC) inducible P450MC, mainly P450c and P450d, than microsomes from LEA rat liver and these isozymes in the LEC were markedly induced by 3-methylcholanthrene treatment. The great difference in cytochrome P450PB content of the liver microsomes between LEC and LEA rats and the maintained constitutive levels of hepatic cytochrome P450MC in the LEC rats suggest a possible role of these cytochrome isozymes in the onset of spontaneous hepatitis and hepatoma.
Carcinogenesis 1989 Nov
PMID:Selective expression and induction of cytochrome P450PB and P450MC during the development of hereditary hepatitis and hepatoma of LEC rats. 280 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>