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

Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.
 ...
PMID:Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1. 17 84

The association between mammary carcinogenesis induced by 7,12-dimethylbenz(alpha)anthracene (DMBA) in the rat, the influence by manipulations of its hepatic metabolism and the secretion of prolactin has been investigated. Various test compounds: coumarin, 4-methylcoumarin, phenobarbital and CCl4 all elevated serum prolactin level, but only coumarin and 4-methylcoumarin reduced tumor incidence. These observations do not support the assumption that the suppression of DMBA-induced breast adenocarcinoma by coumarin and 4-methylcoumarin is mediated via prolactin.
 ...
PMID:Is there any association between elevated serum prolactin level and mammary adenocarcinoma induced by 7,12-dimethylbenz(alpha)anthracene. 80 60

The hypothesis that liver carcinogenesis may have as an important facet the early selection of carcinogen-resistant cells was tested in animals in which putative premalignant hepatocyte populations, hyperplastic nodules, were induced by 2-acetylaminofluorene or by ethionine. Hyperplastic nodules were observed to be resistant to the acute necrogenic effects of 2 hepatotoxins, CCl4 and dimethylnitrosamine, under conditions in which liver cell necrosis occurred in the liver surrounding the nodules. In addition, although [methyl-3H]dimethylnitrosamine was taken up to an equal degree in nodules and normal liver, the interactions with DNA, RNA, and protein in hyperplastic nodules were found to be about 50% less than in control liver. Hyperplastic nodules showed a marked decrease in uptake of [9-14C]-2-acetylaminofluorene, a finding that could account for the large decrease in labeling of DNA, RNA, and protein by [9-14C]-2acetylaminofluorene observed in the nodules. The results are consistent with and support the hypothesis that new hepatocyte populations that appear prior to cancer, during liver carcinogenesis, have as an important biological property a resistance to the cytotoxic effect of hepatocarcinogens. The basis for this resistance might be a decrease in uptake and/or a reduction in the level of activation of carcinogens.
 ...
PMID:The resistance of putative premalignant liver cell populations, hyperplastic nodules, to the acute cytotoxic effects of some hepatocarcinogens. 97 37

The modifying action of chronic liver injury on the process of hepatocarcinogenesis was investigated. To induce cirrhosis or fibrosis F344 rats received CCl4 alone or in combination with phenobarbital, either before (model 1) or after (model 2) the application of initiator, diethylnitrosamine (DENA). In these models, morphology, tumor incidence as well as polysubstrate monooxygenase system, gamma-glutamyltransferase (GGT) and glucose-6-phosphatase (G-6-Pase) were studied. The data presented show that in model 1 the tumor incidence was much lower than in rats treated with DENA alone. This reduction appeared to be associated with the decrease in cytochrome P450 content occurring in model 1 after DENA administration. Promotion of the hepatocarcinogenic process was observed when CCl4 injury followed the application of DENA (model 2). Comparison of marker enzymes in cirrhotic livers and in tumors either with or without cirrhosis indicated that changes in cytochrome P450 and G-6-Pase were rather the results of parenchymal damage, while GGT was elevated only in tumorous livers. In tumorous livers none of the xenobiotic metabolizing activities decreased as much as the cytochrome P450 content of the same samples. Thus conceivably the cytochrome P450 operates more rapidly in tumors than in normal livers.
Carcinogenesis 1992 May
PMID:Modification of DENA-induced hepatocarcinogenesis by CCl4 cirrhosis. Comparison of the marker enzyme patterns. 135 Feb 34

The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression, and significantly enhanced the induction of gamma-glutamyltranspeptidase (GGT)-positive foci and nodules in the CCl4 but not furfural case. Glutathione S-transferase P (GST-P)-positive preneoplastic lesions were not affected. Moreover, phenobarbital (PB) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model, no promotion influence being exerted after treatment with the non-carcinogenic furfural. This study, therefore, suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural.
Carcinogenesis 1992 Aug
PMID:Possible enhancing effect of the immunosuppressive agent, 6-mercaptopurine(6-MP) on focal lesion development in cirrhotic liver induced by carbon tetrachloride but not furfural in F344 rats. 135 82

beta-Carotene protects against photooxidative dermatitis in porphyric humans and mice by quenching of photoactivated species. Other actions of beta-carotene in vivo are explained on the basis of its ability to scavenge free radicals in vitro. For example, in guinea pigs treated with CCl4, beta-carotene decreases pentane and ethane production. Epidemiological studies link low serum beta-carotene levels to elevated risk of lung and other cancers, and in intervention trials, beta-carotene diminishes preneoplastic lesions. However, the dose/response relationships are not well established, and antineoplastic mechanisms await clarification. Given a radical quenching mechanism, beta-carotene should block tumor promotion, but more typically the site of action is progression and an even later role in invasion has not been ruled out. Some antineoplastic actions of carotenoids (such as increased rejection of fibrosarcomas in mice) are attributed to immunoenhancement; others may reflect conversion to retinoids and subsequent gene regulation. Carotenoids other than beta-carotene may act at an earlier stage of carcinogenesis or be more effective as anticarcinogens at certain target sites. As scavengers of hydroxyl radicals, canthaxanthin and astaxanthin are more effective than beta-carotene. Canthaxanthin is sometimes more effective than beta-carotene in chemoprevention, but it is sometimes completely ineffective. Lycopene quenches singlet oxygen more than twice as effectively as beta-carotene. However, the antineoplastic actions of lycopene or astaxanthin remain untested. Explorations of the interactions of carotenoids with other nutrients are just beginning. Dietary fat increases absorption of carotene but decreases antineoplastic effectiveness. Research is hampered by technical problems, including the unavailability of rigorous controls, the instability of carotenoids, and the heterogeneous phase structure induced by hydrophobic compounds in aqueous media. Areas of current controversy and promising approaches for future research are identified.
 ...
PMID:Protection by beta-carotene and related compounds against oxygen-mediated cytotoxicity and genotoxicity: implications for carcinogenesis and anticarcinogenesis. 139 19

The multifactorial nature of carcinogenesis in man has impelled us to study the effects of various chemicals and conditions in combination. In the present investigation, we examined the effects of low doses of 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) in combination with carbon tetrachloride (CCl4) on the formation of glutathione S-transferase placental form (GST-P)-positive foci in rat liver. Administration of diet containing MeIQx at 0.4, 4 or 40 p.p.m., representing one-thousandth, one-hundredth and one-tenth of the dose proved to induce hepatocellular carcinomas (400 p.p.m.), for 8 or 12 weeks did not induce GST-P-positive foci. However, 40 p.p.m. of MeIQx when co-administered with CCl4 (0.7 ml/kg, s.c. twice a week) induced preneoplastic lesions: 7- and 3-fold increases in the numbers and areas of GST-P positive foci in week 8, and 8- and 6-fold increases respectively in week 12, over those with CCl4 alone. Furthermore, a marked increase in the number of hyperplastic nodules was observed in this group of rats in week 12. No significant increases of GST-P-positive foci were observed at doses of 0.4 or 4 p.p.m. MeIQx in combination with CCl4. Thus, it is predicted that chronic exposure to 40 p.p.m. of MeIQx eventually results in induction of hepatocellular carcinomas in injured rat liver.
Carcinogenesis 1992 May
PMID:Induction of preneoplastic lesions by a low dose of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the livers of rats treated with carbon tetrachloride. 158 92

Hemoglobin (Hb) adduct determination by the N-alkyl Edman method was used for in vivo dosimetry of endogenously formed malonaldehyde (MA) and ethene in mice fed diets with different fatty acid composition and induced for lipid peroxidation with carbon tetrachloride (CCl4). In order to amplify lipid peroxidation animals were pretreated with phenobarbital (PB) and the glutathione-depleting agent DL-buthionine-(S,R)-sulfoximine (BSO). Non-treated animals raised on different diets were used as controls. Lipid peroxidation products in liver were measured as 2-thiobarbituric acid reactive compounds (TBA-C). Livers from control mice fed a soya oil based diet (rich in polyunsaturated fatty acids, diet S) showed approximately 6.5-fold higher levels of TBA-C than those from animals raised on a coconut oil based diet (mostly saturated fatty acids, diet C). The level of adducts of MA to Hb, determined as N-(3-hydroxypropyl)valine, was approximately 1.5-fold higher in animals from diet S than in animals raised on diet C. The highest increases in the levels of TBA-C and MA adducts were obtained after a simultaneous treatment of the animals with PB, BSO and CCl4. The increases of TBA-C were 1.3-fold (diet C) and 1.7-fold (diet S). The corresponding increases of MA-Hb adduct levels were 1.3- and 1.6-fold respectively, indicating an increased susceptibility of mice fed diet S to lipid peroxidation. The level of adducts from ethene, determined as N-(2-hydroxyethyl)valine, was also higher in mice from diet S than in animals fed diet C, when all treatment groups were considered. The difference was, however, only slightly significant (P less than 0.02). No difference between control and CCl4-treated animals, with regard to the ethene-Hb adduct, was found. Our results validate the use of Hb dosimetry for monitoring the effects of factors known to influence lipid peroxidation induced in vivo.
Carcinogenesis 1991 Jun
PMID:In vivo hemoglobin dosimetry of malonaldehyde and ethene in mice after induction of lipid peroxidation. Effects of membrane lipid fatty acid composition. 167 Feb 88

Perfluorooctanoic acid (PFOA) is a peroxisome proliferator. The aim of this study was to test for its ability to act as a positive modulator of hepatocarcinogenesis, in the so-called biphasic (initiation by diethylnitrosamine 200 mg/kg ip followed by treatment with the suspected modulators) and triphasic (initiation by the same dose of diethylnitrosamine followed by a selection procedure for 2 weeks consisting of giving 2-acetylaminofluorene and in the middle of this treatment a single dose of CCl4 followed by treatment with the suspected modulators) protocols of liver carcinogenesis. In both protocols treatment with PFOA increased the incidence of malignant hepatocellular carcinoma (HCC). As compared to phenobarbital, the modulating effect of PFOA is more pronounced in a biphasic than in the triphasic protocol. In parallel with positive modulation of HCC, PFOA also selectively induced the peroxisomal acyl-CoA oxidase activity and, to a lesser extent, catalase activity.
 ...
PMID:The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator. 168 73

Multiple alpha-fetoprotein (AFP) RNAs are expressed in the rat liver and are differentially regulated during development. We examined the expression and cellular distribution of the full-length AFP RNA (major form, 2.1 kilobases highly expressed in fetal liver) and 3 variants of 1.7, 1.4, and 1.0 kilobases in normal rat liver, during fetal development, in regeneration, and in carcinogenesis. The 1.7-kilobase variant is expressed only in developing liver (by 15 days of gestation) and is much less abundant than the major form. In adult normal liver the 1.4- and 1.0-kilobase RNAs are the predominant forms. By cell separation studies we show that these variants are produced by parenchymal and nonparenchymal cells in normal rat liver, and that the full-length AFP mRNA is detectable in normal nonparenchymal cells. We demonstrate by in situ hybridization that the 2.1-kilobase mRNA is expressed by some ductular cells and a few nondividing hepatocytes (approximately 1 in 20,000). Further studies revealed that (a) the 2.1-kilobase AFP mRNA encodes translation products of molecular weight 68,000 and 70,000, and probably has multiple sites for translation initiation; (b) the 1.4-kilobase AFP RNA variant in adult rat liver encodes translation products of molecular weight 58,000, 54,000 and 44,000; (c) the 2.1-kilobase AFP RNA increases in liver nonparenchymal cells after CCl4 injury (20-30-fold) and in galactosamine-injured liver (60-100-fold), while the 1.4- and 1.0-kilobase variants change much less; and (d) after partial hepatectomy there are only small changes in any of the AFP RNAs, while during carcinogenesis oval cells contain large amounts of 2.1-kilobase AFP RNA and levels of the 1.4- and 1.0-kilobase species which are lower than those in normal liver. We suggest that after development synthesis of the full-length RNA is not shut off in a small proportion of rat liver cells and that ductular cells that express this RNA may constitute a facultative liver stem cell compartment.
 ...
PMID:Multiple alpha-fetoprotein RNAs in adult rat liver: cell type-specific expression and differential regulation. 171 92


1 2 3 4 5 6 7 8 Next >>