Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) to promote the appearance of gamma-glutamyltranspeptidase-positive (GGT+) foci initiated by diethylnitrosamine (DEN) was studied in a slightly modified Solt and Farber protocol. This protocol consisted of the following treatments: initiation with a single dose of DEN followed by selection/promotion with several non-necrogenic doses of N-OH-AAF and partial hepatectomy. Treatment with N-OH-AAF resulted in a 25-fold increase of the liver volume occupied by GGT+ cells as compared to controls. The role of N-sulfation of N-OH-AAF in the GGT+ foci-selecting activity of N-OH-AAF was studied using the sulfotransferase inhibitor pentachlorophenol (PCP). Inhibition of the N-sulfation pathway with PCP during selection with N-OH-AAF resulted in a greater than 80% decrease in the volume occupied by GGT+ cells, without effects on the number of GGT+ foci generated with this protocol. Also, PCP reduced the number of so called oval and bile duct cells generated by the N-OH-AAF/partial hepatectomy treatment. It is concluded that N-sulfation of N-OH-AAF is responsible for the N-OH-AAF-mediated outgrowth of DEN-initiated hepatocytes to preneoplastic GGT+ foci.
Carcinogenesis 1988 Nov
PMID:The role of N-sulfation in the N-hydroxy-2-acetylaminofluorene-mediated outgrowth of diethylnitrosamine-initiated hepatocytes to gamma-glutamyltranspeptidase-positive foci in male rat liver. 290 38

To better understand the role of free radicals in liver carcinogenesis, endogenous antioxidant defense systems and the susceptibility of membranes to lipid peroxidation were evaluated in early lesions and in malignant tumors induced by the Solt-Farber resistant hepatocyte protocol. These parameters were also measured in the liver surrounding these tumors. In comparison with the normal liver, both nodules and carcinomas show a different biochemical pattern consisting of decreased glutathione peroxidase (GSH peroxidase) and catalase activities plus increased glutathione reductase (GSSG reductase) activity. In contrast, 1 week after the application of the initiation-selection protocol, the liver displays a high level of glutathione (GSH), high GSSG reductase activity, a reduced production of malondialdehyde and no changes in superoxide dismutase and GSH peroxidase activities. These data suggest that the liver is well protected against reactive oxygen species. During the carcinogenic process, the liver parenchyma surrounding the altered foci recovers from most of the modifications induced by the initiation-selection treatment. These results add additional support for the hypothesis that the appearance of early alterations in the liver, after a carcinogenic treatment, might be an adaptive response to a hazardous environment in which selected cell populations are transformed into nodules and/or carcinomas.
Carcinogenesis 1988 Nov
PMID:Analysis of antioxidant defense systems during rat hepatocarcinogenesis. 318 Mar 39

The effect of carcinogenesis on various hepatic microsomal parameters and related cell functions was studied in two tumor models. Hepatocarcinoma was produced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) (Solt-Farber model) and mammary adenocarcinoma using R3230 AC cancer cell line. In these models the effect of the tumor on metabolic functions of hepatocytes was studied. In the DEN/2AAF tumor model in nodules phase I components (cytochrome P-450, aminopyrine N-demethylase, arylhydrocarbon hydroxylase) were reduced, together with microsomal progesterone content and total and specific progesterone binding. Phase II components (glutathione, glutathione S-acyltransferase, UDP-glucuronyl transferase, epoxide hydrolase) were increased. In hepatoma the effects were more enhanced. Nodules grown in the speen retained the dedifferentiated enzyme characteristics. In the R3230 AC mammary adenocarcinoma phase I components of the hepatic endoplasmic reticulum were reduced, and phase II components increased. Progesterone content and receptor binding were also increased. These results indicate that enzymatic abnormalities in the liver cell are connected with cancer production and the hepatic dedifferentiation seems to be indistinguishable in tumor-bearing liver from those seen with extrahepatic neoplasms.
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PMID:Hepatic metabolism and carcinogenesis. Its role in hepatoma and adenocarcinoma. 338 80

The induction of a novel Ca2+-dependent protease in rat liver treated with various liver promoters, as well as its increase in preneoplastic lesions during liver carcinogenesis, was demonstrated. Six groups of male Fischer 344 rats (150 g body weight) were fed separately diets containing one of the following promoters: 0.05% phenobarbital (PB), 0.05% dichlorodiphenyltrichloroethane (DDT), 0.25% ethyl-alpha-chlorophenoxyisobutyrate (CPIB), 0.5% butylated hydroxytoluene (BHT), 10 ppm 17-alpha-ethynylestradiol (EE), and 0.05% of the non-promoter diphenylhydantoin (DH). After feeding the indicated diets for 1 week, rats were killed and protease activity in the microsomal fraction of liver tissue was determined using N-benzoyl-L-tyrosine ethyl ester as substrate. The activity of protease increased 3- to 5-fold after treatment with the promoters and compared with normal liver; the non-promoter (DH) induced a slight increase in activity. Hyperplastic nodules were induced according to the method of Solt and Farber. The activity of protease was significantly high in these preneoplastic lesions compared with the surrounding liver tissue. Biochemical characterization of this protease revealed the following properties: high Ca2+ dependency, different molecular weight and optimum pH from previously reported proteases, and preferential distribution in the SER fraction. These results suggest that a novel type of protease is induced specifically in the liver by promoters of liver carcinogenesis. The possible importance of this protease in the carcinogenic process is discussed.
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PMID:Induction of a novel Ca2+-dependent serine protease in rat liver treated with various promoters of liver carcinogenesis. 355 69

Dietary 2-acetylaminofluorene (2-AAF) coupled with a stimulus for cell proliferation such as a 2/3 partial hepatectomy (PH) or a necrotizing dose of carbon tetrachloride is frequently employed to generate nodules of resistant ("initiated") rat hepatocytes. This regimen is a useful model for experimental analysis of alterations in hepatocytes during carcinogenesis, and also as an assay for initiation by various carcinogens. Because of the decreasing availability of carcinogen-containing diets from commercial sources, we have developed alternative methods of 2-AAF administration to generate nodules in rats initiated with N-nitrosodiethylamine. This study compared the nodule-selecting and cancer-promoting efficacy of 2-AAF administered by the Solt-Farber procedure (0.02% in diet for 2 weeks) with 2-AAF administered by gavage, as a suspension in 1% aqueous carboxymethyl-cellulose (CMC). Three or 4 daily administrations of 2-AAF by gavage (20 mg/kg/day) followed by PH on day 4 were equivalent to the dietary regimen in generating early resistant nodules, late persistent nodules and hepatocellular carcinomas. These regimens were similar to the dietary regimen of 2-AAF in inhibiting virtually all normal hepatocyte proliferation. These regimens permit control over the duration and level of 2-AAF exposure and the resulting size of selected nodules.
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PMID:Alternative methods of selecting rat hepatocellular nodules resistant to 2-acetylaminofluorene. 367 91

The quantitative distribution of Kupffer cells was measured in the liver of Fischer-344 male rats during the course of chemical hepatocarcinogenesis according to the Solt-Farber model, i.e. an initiating agent, a selective mitogenic inhibitor and a strong proliferation stimulus were applied subsequently. Pre-neoplastic and neoplastic lesions were followed up to 17 months. Kupffer cells were detected by the phagocyted carrageenan stained with toluidine blue and were counted using the ocular square in the light microscope. In the non-transformed areas of the liver of treated rats the number of Kupffer cells was generally different from the values of untreated controls. The altered cell foci contained fewer Kupffer cells than the normal untreated rats and the non-transformed liver areas, while in hepatocellular carcinomas there was a high reduction in the number of detectable Kupffer cells. The number of Kupffer cells was variable around and within neoplastic nodules. While Kupffer cells do not follow the neoplastic proliferation of hepatocytes during hepatocarcinogenesis, it is possible that humoral factors are produced by transformed hepatocytes against Kupffer cells.
Carcinogenesis 1986 Aug
PMID:Quantitative light microscopic study on the distribution of Kupffer cells during chemical hepatocarcinogenesis in the rat. 373 89

Rat liver carcinogenesis was induced according to the resistant hepatocyte model of Solt and Farber. One week after the end of the procedure for the rapid growth of altered hepatocytes, one group of rats was submitted to a high fat (20%) regimen up to the end of the experiment. The incidence of histologically confirmed malignant hepatocarcinomas was compared with that observed in a group that remained on a normal diet. The modulating (promoting) effect of the high fat regimen was evident since nine out of 10 animals in this group bore macroscopically detectable tumors and eight out of 10 presented histologically confirmed hepatocellular carcinomas as early as 24 weeks after the beginning of the experiment. At that time, no malignant tumors were detected in the group submitted to the normal fat regimen. These results are similar to those resulting from a porto-caval shunt or the chronic administration of liver tumor promoters. This suggests that at this stage of the carcinogenic process, any treatment inducing chronically metabolic adaptation in a tissue containing preneoplastic nodules modulates positively the progression of these lesions as demonstrated by the dramatic reduction of the lag period for their malignant transformation.
Carcinogenesis 1987 Feb
PMID:Dietary modulation of rat liver carcinogenesis. 380 21

A chronic 8 to 11 week administration of the hepatic tumor promoter phenobarbital (0.05% in drinking water) to rats previously subjected to the initiation:selection process of Solt and Farber was found to further increase the gamma-glutamyl transpeptidase activity of individual hyperplastic liver nodules of 4.0-10.0 mm in diameter over comparably sized nodules from control livers. Those rats which received 11 weeks of the chronic phenobarbital treatment also showed a significant increase in their liver wet weights. In addition, random tissue samples of non-nodular liver taken from the 11 week phenobarbital-treated rats exhibited a gamma-glutamyl transpeptidase mean specific activity which was approximately 3 times higher than that of control non-nodular liver samples. In contrast, there was a 1.5-fold increase in the mean % gamma-glutamyl transpeptidase-positive area (cm2), as determined histochemically, in cryostat sections made from non-nodular samples of the 11 week phenobarbital-treated rats when compared with that of control liver sections. Interruption of the chronic phenobarbital administration at 8 weeks followed by 3 weeks of control treatment resulted in a reversal of the gamma-glutamyl transpeptidase activity response shown by the hyperplastic liver nodules and non-nodular liver tissue samples. Thus, phenobarbital can quantitatively modulate gamma-glutamyl transpeptidase activity in carcinogen-induced hyperplastic liver lesions in the rat during the early stages of hepatocarcinogenesis.
Carcinogenesis 1984 Dec
PMID:Effect of chronic phenobarbital administration on the gamma-glutamyl transpeptidase activity of hyperplastic liver lesions induced in rats by the Solt/Farber initiation: selection process of hepatocarcinogenesis. 614 21

A 1-week treatment with the hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (ZAMI 1305) induces the appearance of preneoplastic liver lesions--oval cell hyperplasia, basophilic and gamma-glutamyltranspeptidase positive (GGT+) foci--in female Wistar rats, as evidenced by the Solt and Farber short-term test of carcinogenesis. ZAMI 1305-treatment also induces liver DNA damage, as evaluated by alkaline sucrose gradient analysis. The data suggest that the oncogenic B-blocker ZAMI 1305 has initiating activity in the liver of the female Wistar rat.
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PMID:Tumor-initiating activity of the beta-blocker ZAMI 1305 in the liver of the female Wistar rat. 615 20

Endogenous (estradiol-17 beta; progesterone) and synthetic (ethinyl estradiol; cyproterone acetate; norethindrone acetate; norethynodrel) sex steroids were evaluated for tumor-initiating activity in the rat liver using the Solt-Farber system. All steroids were negative. This provides further evidence that tumor formation in long-term rodent bioassays by these compounds may be due to epigenetic mechanisms.
Carcinogenesis 1983
PMID:Assay of some endogenous and synthetic sex steroids for tumor-initiating activity in rat liver using the Solt-Farber system. 621 32


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