The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.
Animals ; Capsaicin/pharmacology/*toxicity ; Cocarcinogenesis ; Diethylnitrosamine ; Liver Neoplasms, Experimental/chemically induced/prevention & control ; Lung Neoplasms/chemically induced/prevention & control ; Male ; Methylnitrosourea ; Neoplasms, Experimental/*chemically induced/prevention & control ; Nitrosamines ; Rats ; Rats, Inbred F344 ; Urinary Bladder Neoplasms/chemically induced

The present study was designed in order to investigate the lectin induced cytoagglutination properties of normal and transformed cells and surface alterations in the early stage of the transformed cells by characterizing the structural changes on the hepatoma surface membrane. Rat and rabbit erythrocytes and Sarcoma 180 ascites tumor cells were used for the lectin-induced cytoagglutination. Plotting % agglutination versus concanavalin A(Con A) concentration, sigmoid curves appeared in all cases. alpha-methyl-D-mannopyranoside(alphaMM) inhibited Con A induced cytoagglutination and the degrees of inhibition depended on the cell types and species. When rats were fed a diet containing 0.06% 3'-methyl-4dimethylaminoazobenzene(3'-Me DAB) for 12 weeks, almost all of the rats had solid liver tumors. Polyacrylamide gel electrophoresis of surface membrane proteins of these rat livers and of transplanted tumor cells showed three distinct protein bands, of which two were absent in normal rat livers. The molecular weights of these proteins were 73,000, 66,000, and 57,000 daltons. Antiserum against primary hepatocarcinoma surface proteins precipitated with three membrane proteins obtained from primary hepatocarcinoma cells as well as transplanted hepatocarcinoma cells, suggesting the presence of specific tumor antigens in these cells.
Animal ; Cell Membrane/pathology* ; Cell Transformation, Neoplastic/ultrastructure* ; Concanavalin A/diagnostic use ; Liver Neoplasms, Experimental/chemically induced ; Liver Neoplasms, Experimental/ultrastructure* ; Methyldimethylaminoazobenzene ; Rabbits ; Rats ; Surface Properties

Iron is essential for the growth of all living cells. One of the most important intracellular roles of iron is the activation of ribonucleotide reductase, which is indispensible to the production of deoxyribonucleotide necessary for DNA synthesis. Deferoxamine (DFO) is an iron chelating agent and has been known to have an antiproliferative effect in various malignant cells including hepatocellular carcinoma and the effect seems to be related to depletion of iron. This study was undertaken to investigate the effect of DFO on preneoplastic lesions in chemically induced hepatocarcinogenesis. The resistant hepatocyte model was used and Sprague Dawley rats were divided into the following groups; I: normal control, II: carcinogen administered group, III: carcinogen and DFO administered group. Rats were sacrificed at 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks and 8 weeks after partial hepatectomy (PH). DFO (50 mg/kg/day, I.P.) was daily injected from 3 weeks before administration of carcinogen to the time when rats were sacrificed. Hepatic iron content was higher in group II than in group III, especially at 3 days and 1 week after PH. Hyperplastic lesions of resistant hepatocytes were less well developed in group III than in group II. Bromodeoxyuridine labelling indices of oval cells and hyperplastic lesions of resistant hepatocytes were higher in group II than in group III except for rats examined at 3 days after PH. The results suggest that DFO has an antiproliferative effect on preneoplastic lesions in hepatocarcinogenesis and it might be related to reduction of the hepatic iron.
Animal ; Deferoxamine/*pharmacology ; Diethylnitrosamine ; Liver Neoplasms, Experimental/chemically induced/*prevention & control ; Male ; Precancerous Conditions/chemically induced/*prevention & control ; Rats ; Rats, Sprague-Dawley ; Support, Non-U.S. Gov't

OBJECTIVETo understand the molecular mechanism and find out the responsible genes for liver cancer by exploring the regulation of gene expression during hepatocarcinogenesis in tree shrew induced by aflatoxin B1 (AFB1).

METHODSThe tissues from tree shrew of different stages during the pathogenesis and development of hepatocellular carcinoma (HCC), liver cancer tissue, para-cancerous tissues, pre-cancerous liver tissues, liver tissues of the same stage from normal controls and the liver tissues taken before AFB1-treatment were analyzed for gene expression by cDNA array.

RESULTSFour patterns of gene expression were observed during AFB1-induced hepatocarcinogenesis. They were: genes up-regulated in HCC tissue and para-cancerous tissue, especially in HCC tissues; genes with similar expressing level in both HCC tissue and para-cancerous tissue, but higher than that in pre-cancerous tissue; genes down-regulated in HCC tissue; genes up-regulated before HCC appeared but down-regulated after HCC appeared.

CONCLUSIONDynamic observation of gene expression will be beneficial to elucidate the mechanisms of AFB1- induced hepatocarcinogenesis and locate the responsible genes.

Aflatoxin B1 ; toxicity ; Animals ; Gene Expression Profiling ; Liver Neoplasms, Experimental ; chemically induced ; genetics ; Oligonucleotide Array Sequence Analysis ; methods ; Tupaiidae

OBJECTIVETo investigate the role of the spleen on hepatocyte proliferative activity during experimental hepatocarcinogenesis in rats.

METHODSCell-cycle and expression of proliferating cell nuclear antigen (PCNA) of hepatocytes were studied by immunohistochemical and flow cytometric technique in two groups: splenectomy (45 rats) and sham-operation with laparotomy (45 rats).

RESULTS(1) Hepatocirrhosis was formed in group A earlier than in group B. Marked degenerative changes of the liver parachyma showing vacuolization of hepatocytes were observed in hepatic lobules. (2) The proliferative level of hepatocytes increased with the progression of hepatocarcinogenesis, and topped at the 18 th week. (3) The proliferative level of the splenectomy group was lower than that of the sham-operation group in the mid-stage of carcinogenesis (t = 4.76, P < 0.05). After stopping feeding diethylnitrosamine (DENA), however, no difference was found in the hepatocyte proliferative activity between the two groups at the 18th week.

CONCLUSIONSThere is a close relationship between hepatic proliferative activity and spleen, and the spleen may play an important role in facilitating hepatic proliferation.

Animals ; Cell Cycle ; Diethylnitrosamine ; Liver ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; pathology ; Male ; Proliferating Cell Nuclear Antigen ; analysis ; Rats ; Rats, Wistar ; Spleen ; physiology ; Splenectomy

Anticarcinogenic effect of red ginseng (Panax ginseng C.A. Meyer cultivated in JiLin, China) on the development of liver cancer induced by diethylnitrosamine (DEN) in rats was studied, especially in preventive and curative groups. In the preventive group, the rats were given with DEN concomitantly with red ginseng fluid, and in the curative group, the rats were administered with red ginseng fluid after they developed liver cancer nodules induced by DEN. The result of the preventive group revealed that the developmental rate of liver cancer in the experimental group was 14.3%, while 100% in the control group, with the difference being statistically significant. DNA, RNA, glycogen, gamma-GT, SDH, and 5'-NT were maintained at relatively normal level in experimental group, and decreased or increased in the control group. The result of curative group showed that hepatoma nodules of the DEN-red ginseng group I were smaller than those of control group I, the structure of hepatic tissue was well preserved, the area with gamma-GT positive was smaller, and the ultrastructure of hepatocytes was normal. The average life span the DEN-red ginseng group II and the DEN control group II were 72.8 and 42.3 days, respectively. To sum up, all findings on preventive and curative groups had clearly proved that the red ginseng had the anticarcinogenic effect on the development of liver cancer induced by DEN in rats.
Animal ; Anticarcinogenic Agents/*pharmacology ; Carcinoma, Hepatocellular/chemically induced/*pathology ; Data Interpretation, Statistical ; Diethylnitrosamine/adverse effects ; Liver/pathology/ultrastructure ; Liver Neoplasms, Experimental/chemically induced/*pathology ; Male ; *Panax ; Plant Extracts/pharmacology ; Rats ; Rats, Wistar

2-Acetylaminofluorene ; Angiogenesis Inhibitors ; pharmacology ; Animals ; Carcinoma, Hepatocellular ; chemically induced ; metabolism ; pathology ; Immunohistochemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; metabolism ; pathology ; Male ; NF-kappa B ; antagonists & inhibitors ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thalidomide ; pharmacology

Animals ; Antineoplastic Agents ; therapeutic use ; Chromans ; therapeutic use ; Diethylnitrosamine ; Ligands ; Liver Neoplasms, Experimental ; chemically induced ; drug therapy ; Male ; PPAR gamma ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Thiazolidinediones ; therapeutic use

Three different chemical carcinogens, 2-acetylaminofluorene (AAF), diethylnitrosamine(DENA), and 3'-methyl-4dimethylaminoazobenzene (3'-Me DAB) were used to induce hepatomas in rats. Plasma membrane surface proteins of normal rat liver cells and rat hepatomas were extracted with 3M KCI. From the analysis of the proteins of normal rat liver and rat hepatoma induced by 3'-Me DAB by discontinuous polyacrylamide gel electrophoresis(Disc-PAGE), under nonreducing and nondenaturing conditions polyacrylamide gel electrophoresis in the presence of SDS and 2-mercaptoethanol (SDS-PAGE), Sephadex G-200 gel permeation chromatography, DEAE-A50 ion-exchange chromatography and two-dimensional gel electrophoresis, at least three tumor specific antigens were identified. One had a molecular weigh of 66,000 (pl=6.79) while the other two had the same molecular weight 73,000 but differed in their isoelectric points (7.58 and 7.81). For immunological analysis of tumor specific antigens, the absorbed antiserum was prepared. Plasma membrane surface proteins of rat hepatoma induced by 3'-Me DAB were used to obtain New Zealand White male rabbit antiserum. Rabbit antiserum was then reacted with the proteins isolated from the plasma membrane surface of normal rat liver and the absorbed antiserum reacting specifically with the tumor specific antigens derived by 3'-Me DAB was obtained. Using the absorbed antiserum, the immunoreactivities of plasma membrane surface proteins isolated from rat hepatomas induced by 3'-Me DAB, AAF, and DENA were compared by Ouchterlony double immunodiffusion analysis and immunoelectrophoresis. To characterize the proteins reacting to the absorbed antiserum, immunoglobulin G was separated from the absorbed antiserum and coupled to cyanogen bromide-activated Sepharose CL-4B. The isolated proteins from the plasma membrane surface proteins of 3'-Me DAB-induced hepatoma using this immunoaffinity chromatography had molecular weights of 66,000 and 73,000. The localization of these proteins on surface plasma membranes of rat hepatomas induced by 3'-Me DAB was confirmed by an immunofluorescence technique. The experimental results revealed the existence of cross-reacting common antigens on the plasma membrane surface of rat hepatomas induced by different hepatocarcinogens.
2-Acetylaminofluorene ; Animal ; Antigens, Neoplasm/*isolation and purification ; Antigens, Surface/isolation and purification ; Diethylnitrosamine ; Liver Neoplasms, Experimental/chemically induced/*immunology ; Methyldimethylaminoazobenzene ; Rats ; Rats, Inbred Strains ; Support, Non-U.S. Gov't

In summarizing the results of the experimental studies up to the present, it is conjectured that the pathogenicity of Entamoeba histolytica or establishment of amoebiasis is not unique but differs by strain and age of Entamoeba histolytica and the age of the host. A non-virulent strain is more likely adapt to as low a temperature as 32 . This is not so in the strains which originated form clinical cases. Iso-enzyme patterns may roughly characterize pathogenic strains from non-pathogenic, Red blood cells may contribute as nutrients for growth of Entamoeba histolytica only after they have been hemolysed, but they are toxic to the amoebae as long as they remains intact. A low protein diet and stress may facilitate the establishment of amoebiasis; male sex hormones or previous infection by enteric bacteria provide a more advantageous condition than the female; and hepatotoxic agents will accelerate amoebic hepatitis.
2-Acetylaminofluorene ; Animal ; Antigens, Neoplasm/*isolation and purification ; Antigens, Surface/isolation and purification ; Diethylnitrosamine ; Liver Neoplasms, Experimental/chemically induced/*immunology ; Methyldimethylaminoazobenzene ; Rats ; Rats, Inbred Strains ; Support, Non-U.S. Gov't