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)

The effects of crocetin pretreatment on both hepatic aflatoxin B1 (AFB1)-DNA binding and AFB1 hepatotoxicity in rats has been examined. For these studies, male Wistar rats were treated with AFB1 (2 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma-glutamyltranspeptidase. After pretreatment of the animals with crocetin (2 or 6 mg/kg) daily for three consecutive days, the enzyme elevations were significantly suppressed. This suggested that the crocetin possessed chemopreventive effects on the early acute hepatic damage induced by AFB1. Under these experimental conditions, consistent elevations of hepatic glutathiones (GSH) and activities of glutathione S-transferase (GST) and glutathione peroxidase (GSH-Px) were observed. Crocetin treatment also decreased AFB1-DNA adduct formation in AFB1-treated animals. From these results, we suggest that the protective effect of crocetin on AFB1 hepatotoxicity in rats might be due to the hepatic tissues' defense mechanisms that elevated the cytosol GSH and the activities of GST and GSH-Px.
Carcinogenesis 1991 Mar
PMID:Effects of crocetin on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats. 167 27

The effect of di(2-ethylhexyl)phthalate (DEHP) on diethylnitrosamine (DEN)-initiated preneoplastic liver lesions with expression of gamma-glutamyltranspeptidase (GGTase) and loss of adenosine triphosphatase (ATPase) as well as alterations of hepatic carbohydrate metabolism in male and female Sprague-Dawley rats have been investigated. Two treatment schedules have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic islands and by the biochemical determination of alterations in enzyme activities of liver homogenates and of serum, the last indicating hepatotoxicity. For initiation, a single dose of DEN was given, followed by treatment with various doses of DEHP given three times weekly by gavage for 7 or 11 consecutive weeks. As histochemical enzyme markers, the expression of positive GGTase as well as the deficiency in ATPase were used for identification of liver foci. The weanling female rats (protocol A) were found to be more sensitive to the carcinogenic effect of DEN in view of foci incidence than the mature male rats which underwent partial hepatectomy prior to DEN application. The administration of 200 mg DEHP/kg body wt increased the incidence of ATPase-deficient foci in both male and female rats; however, concentrations of 1000 and 2000 mg DEHP/kg decreased the incidence of liver foci. The number of foci with expression of GGTase was only slightly increased in female rats following a DEHP concentration of 50 mg/kg, and 200 mg/kg body wt. DEHP alone did not induce preneoplastic lesions that could be identified by these two markers. Biochemical investigations indicate that DEHP alters the metabolic pattern in liver. An increase of the NADP-linked enzymes glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme, extra-mitochondrial ICDH as well as an enhancement of NAD-dependent alpha-G3PDH and lactate dehydrogenase were found following DEHP administration. On the other hand the glycolytic enzymes pyruvate kinase (PK) and enolase as well as the gluconeogenetic enzyme fructose-1,6-bisphosphatase (FBPase) were significantly reduced. In protocol B (male rats) the reactions of PK, FBPase and malic enzyme were more altered after DEHP exposure than in protocol A, while the activity of G6PDH was more increased in protocol A. Most enzymes being involved in the carbohydrate metabolism are influenced by DEHP in a dose-dependent manner. There was no increase in serum FBPase activity in both male and female rats after DEHP treatment but a reduction of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase activities was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1990 Dec
PMID:Di(2-ethylhexyl)phthalate alters carbohydrate enzyme activities and foci incidence in rat liver. 197 36

An antioxidant fraction of Chinese green tea (green tea antioxidant; GTA), containing several catechins, has been previously shown to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in mouse skin. In the present study, GTA was shown to have antioxidative activity toward hydrogen peroxide (H2O2) and the superoxide radical (O2-). GTA also prevented oxygen radical and H2O2-induced cytotoxicity and inhibition of intercellular communication in cultured B6C3F1 mouse hepatocytes and human keratinocytes (NHEK cells). GTA (0.05-50 micrograms/ml) prevented the killing of hepatocytes (measured by lactate dehydrogenase release) by paraquat (1-10 mM) and glucose oxidase (0.8-40 micrograms/ml) in a concentration-dependent fashion. GTA (50 micrograms/ml) also prevented the inhibition of hepatocyte intercellular communication by paraquat (5 mM), glucose oxidase (0.8 micrograms/ml), and phenobarbital (500 micrograms/ml). In addition, GTA (50 micrograms/ml) prevented the inhibition of intercellular communication in human keratinocytes by TPA (100 ng/ml). Cytotoxicity and inhibition of intercellular communication, two possible mechanisms by which tumor promoters may produce their promoting effects were therefore prevented by GTA. The inhibition of these two effects of pro-oxidant compounds may suggest a mechanism by which GTA inhibits tumor promotion in vivo.
Carcinogenesis 1989 Jun
PMID:Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. 247 May 25

Isolated trout liver cells were treated with lysolecithin to produce an in situ system for characterizing DNA repair in teleosts. In this preparation, the integrity of the plasma membrane is altered, nuclei remain intact, and the concentrations of dNTPs and nucleotide analogs, which normally do not penetrate intact plasma membranes, can be controlled. Following lysolecithin treatment, 50% of the total cellular protein and nearly 75% of total lactate dehydrogenase activity was released from the liver cells. Microscopic examination indicated that the integrity of the plasma membrane of trout hepatocytes was disrupted by lysolecithin; however, smaller nonhepatocytic liver cells were resistant to the disrupting effects of this detergent. Bleomycin induced DNA repair synthesis in lysolecithin-treated cells, as demonstrated by CsCl gradient analysis of 5-bromo, 2'-deoxyuridine, 5'-triphosphate-labeled DNA. Optimal conditions for bleomycin-induced DNA repair synthesis in lysolecithin-treated trout liver cells were considerably different from that in lysolecithin-treated mammalian cells. Bleomycin-induced DNA repair synthesis was lower in lysolecithin-treated trout liver cells than in lysolecithin-treated mammalian cells at identical concentrations of 2'-deoxyribonucleoside, 5'-triphosphates (dNTPs), suggesting the decreased sensitivity of trout cells in unscheduled DNA synthesis assays can be attributed to factors other than differences in dNTP pools. Bleomycin-induced DNA repair synthesis in trout hepatocytes was shown to be very sensitive to inhibition by 2', 3'-dideoxythymidine, 5'-triphosphate and was resistant to inhibition by cytosine arabinoside, 5'-triphosphate, butylphenyldeoxyguanosine, 5'-triphosphate and aphidicolin. These observations indicate repair of bleomycin-induced DNA damage in trout cells occurs through a mechanism similar to that in mammalian cells, utilizing DNA polymerase beta.
Carcinogenesis 1989 Jun
PMID:DNA repair synthesis in isolated rainbow trout liver cells. 272 Sep 10

This paper describes in vitro studies on the effects of environmental pollutants (SO2/NOx) in biological systems. Basic physical, chemical and biochemical parameters were analyzed to establish the rate of SO2/NOx absorption by the culture medium. It was shown that the pH remains constant for 24 h of exposure to gas concentrations up to 50 p.p.m. The concentration of ions resulting from absorption of each pollutant in the liquid phase is dependent on their concentration in the gas phase and on exposure time. Short exposure times and high gas dosages resulted in similar doses in the medium as long exposure periods and low gas dosages. The activities of a human serum standard (alkaline phosphatase, ALP; aspartate amino transferase, AST; alanine amino transferase, ALT; gamma-glutamyltransferase, gamma-GT; lactate dehydrogenase, LDH) were determined after gaseous exposure to SO2 and NOx. The results revealed a distinct decrease in the activity of LDH after 1, 3 and 5 h exposure to 200 p.p.m. SO2. The effects of the pollutants were assayed in vitro using fetal hamster lung cells (FHLC), rat hepatocytes and the cell line CO60. For the determination of toxic effects, it was shown that the plating efficiency was a more sensitive parameter than the assay for trypan blue exclusion. Toxicity indicated as an increase of LDH leakage was not observed from FHLC in culture. Instead, a decrease of LDH was found following SO2 exposition. This decrease was similar to that observed for the human serum standard. The induction of DNA single-strand breaks was determined as a measure of genotoxic effects. SO2 application decreased the rate of DNA single-strand breaks induced by N-nitroso-acetoxymethyl-methylamine in both FHLC and in rat hepatocytes. SO2 or NOx treatment of CO60 cells for 1 h did not result in the induction of DNA amplification. HSO3- added directly to the medium as the sodium salt, however, distinctly induced the amplification of SV40 DNA. The amplification rates induced by benzo[a]pyrene or dimethylbenzanthracene were neither influenced by SO2, NOx nor HSO3-. An additive effect of HSO3- with either benzo[a]pyrene or dimethylbenzanthracene for this biological parameter was therefore not observed.
Carcinogenesis 1988 Jul
PMID:Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. I. In vitro studies. 283 97

Short term in vivo studies were performed to study biological effects of the common air pollutants SO2 or NOx and their influence on the genotoxic activities of nitrosamines. Hepatocytes and lung cells were isolated from Sprague-Dawley rats which had inhaled 50 p.p.m. of SO2 or NOx for 2 weeks. After incubating the cells for 1 h, genotoxicity was determined in hepatocytes by measuring DNA single-strand breaks induced by N-nitroso-acetoxymethylmethylamine, N-nitrosodimethylamine and N-nitrosomethylbenzylamine. Parameters of toxicity (trypan blue exclusion and leakage of serum enzymes) were determined in both liver and lung cells also following 1 h incubation. The activities of aryl hydrocarbon hydroxylase (AHH), nitrosodimethylamine demethylase (NDMA-D) and glutathione-S-transferase (GST) were determined in subcellular microsomal fractions isolated from lung and liver tissues. Finally, as a measure of overall toxicity, the activities of various serum enzymes were determined in the blood serum of the rats. It was found that the induction of DNA single-strand breaks by three nitrosamines was decreased in hepatocytes from SO2-treated animals. The viability of rat hepatocytes and of rat lung cells, as determined by trypan blue exclusion, was similar in all three treatment groups immediately after isolation, as well as after 1 h incubation with DMSO or with the nitrosamines. In contrast, the leakage of enzymes was different in hepatocytes of SO2-treated rats, since lactate dehydrogenase activity was decreased. Leakage of enzymes from the lung cells did not differ from group to group, but was lower than from hepatocytes. Foreign compound metabolizing enzymes were mainly decreased in NOx-treated animals, namely AHH, NDMA-D and GST in liver and GST in the lung. For SO2-treated animals NDMA-D was increased in liver and GST was decreased in lung. Blood serum enzyme levels were not greatly different from each other, except for lactate dehydrogenase which was elevated in SO2-exposed animals.
Carcinogenesis 1988 Jul
PMID:Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. II. Short term in vivo studies. 289 5

The isoenzyme patterns of lactate dehydrogenase (LDH), hexokinase, phosphofructokinase, and aldolase were investigated in cultured normal and carcinogen-treated human endometrial stromal cells. Both normal and carcinogen-treated cells had similar phosphofructokinase and aldolase isoenzymes. Distinctive changes in hexokinase and LDH isoenzyme patterns were found in the carcinogen-treated stromal cells. The LDH isoenzyme patterns of the carcinogen-treated stromal cells were shifted toward the muscle LDH forms. This is comparable to the alteration of LDH isoenzyme profiles observed in cell lines established from human uterine sarcomas. The two tissue culture media used affected the LDH isoenzyme patterns of endometrial stromal cells but differences between the LDH isoenzyme patterns of control and carcinogen-treated cells were detected regardless of the growth medium used. Total LDH activity was not significantly different in control and carcinogen-treated stromal cells. The hexokinase isoenzyme patterns expressed by the carcinogen-treated stromal cells were distinctly different from the normal hexokinase patterns. The treated stromal cells contained both hexokinase I and II, whereas the normal cells contained only hexokinase I. Hexokinase and LDH isoenzyme patterns may serve as markers with which to evaluate carcinogen-induced neoplastic changes in cultured endometrial stromal cells.
Carcinogenesis 1985 Feb
PMID:Analysis of isoenzymes in normal and carcinogen-treated human endometrial stromal cells in culture. 315 3

It has been proposed that increased rates of hepatic hydrogen peroxide (H2O2) production may initiate or promote the liver tumors that appear following chronic exposure of rodents to chemicals that cause peroxisome proliferation. However, the effect of H2O2 on the structural integrity of DNA in parenchymal hepatocytes, the target cells of peroxisome proliferator-induced carcinogenesis, is largely uncharacterized. Furthermore, oxidant-induced cellular damage has been invoked as causal of a number of hepatotoxic effects associated with exposure to chemicals other than peroxisome proliferators. For these reasons, alkaline elution analysis was used to study the action of H2O2, added exogenously, on DNA of intact, isolated rat hepatocytes. Addition of a bolus of H2O2 (0.01-1.0 mM) to monolayer cultures of hepatocytes caused concentration-dependent increases in single-strand DNA breaks (SSDB), which were maximal within 30 min of exposure. Cytotoxicity, as measured by lactate dehydrogenase (LDH) release, was minimal during a 1-h exposure to H2O2 concentrations less than 1 mM, but the efflux of oxidized glutathione was increased. Formation of SSDB was nearly linear with respect to H2O2 concentration in the range 0.1-1.0 mM. No double-strand DNA breaks or DNA-protein crosslinks were identified at H2O2 concentrations of 1 mM or less. Repair of SSDB in H2O2-free medium occurred in a rapid, linear manner only for the first 15 min, resulting in disappearance of 65% of the SSDB. A second, slower phase of SSDB rejoining occurred between 20 and 60 min of incubation in H2O2-free media; at 60 min rejoining was maximal (80% repair). These results define a specific type of DNA damage associated with H2O2 exposure of hepatocytes and suggest that primary cultures of rat hepatocytes are a suitable model for characterizing the potential genotoxic effects of oxidants, particularly excess H2O2 that may occur in the livers of animals exposed chronically to peroxisome proliferators.
 ...
PMID:DNA strand breaks induced by hydrogen peroxide in isolated rat hepatocytes. 335 84

Aflatoxin carcinogenesis appears to relate to multiple factors. This includes bulky adduct formation at DNA guanine N-7. The process also requires more extensive physiological degradation, possibly by the toxin alone as the active principle, but in instances also involving other assaults (e.g., hepatitis B virus). Since aflatoxin carcinogenesis involves complex effects, we have undertaken to define the range of influence of this common food contaminant upon a susceptible model, the broiler-type chick. Aflatoxicosis in two treated groups was indicated by jaundice, coagulopathy, dehydration of combs and shanks, retardation of body weight, and decrease in bursa weight. Blood clotting time, hemoglobin content, erythrocyte and packed-cell volume were affected. Hepatocytes were swollen and had undergone fatty degeneration. Bile duct hyperplasia was evident. Total serum protein, alkaline phosphatase, creatine, lactate dehydrogenase, serum glutamic oxalacetic transaminase and glutamyl transpeptidase were similarly abnormal in birds receiving the contaminated (0.5 and 2.5 micrograms/g aflatoxin B1) feed rations. The aflatoxin B1 and its metabolites were isolated by HPLC from chick serum, liver and muscle.
 ...
PMID:Clinical and biochemical effects of aflatoxin in feed ration of chicks. 392 39

Chronic treatment with 0.1 microM diethylstilbestrol (DES) increased the expression of phenotypic alterations in human endometrial stromal cells pretreated with the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Abnormal morphology, expression of gamma-glutamyltranspeptidase, and the ability to form colonies under restrictive conditions were more pronounced after combined treatment with carcinogen and DES compared to carcinogen or DES alone. This effect did not appear to be due simply to growth enhancement by DES, because acute treatment with DES did not alter colony formation, growth rate or thymidine incorporation into DNA in stromal cell cultures. Neither did the presence of DES after the toxicity of MNNG. DES did cause shifts in the isoenzyme distribution of lactate dehydrogenase which could be indicative of a hormonal response. The results suggest that DES may act as a tumor promoter or cocarcinogen in human cells through a mechanism other than simply stimulating cell proliferation, but that other estrogenic effects may contribute to the promotional process.
Carcinogenesis 1984 May
PMID:Promotional effect of diethylstilbestrol on human endometrial stromal cells pretreated with a direct-acting carcinogen. 614 1


1 2 3 4 5 6 7 8 9 Next >>