Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochemical and histochemical studies were conducted in aflatoxin B1-induced liver tumors in adult rainbow trout. Specific activities of the phase I enzymes, ethoxyresorufin-O-deethylase (EROD), microsomal and cytosolic epoxide hydrolase (mEH and cEH), aldehyde dehydrogenase (ALDH) and DT-diaphorase, and the phase II enzymes, gamma-glutamyltransferase (gamma-GT), glutathione transferase (GST) and uridine diphosphoglucuronyl transferase (UDPGT) were measured. Cryostat sections of tumor and surrounding liver from the same cohorts were analyzed immunohistochemically for cytochrome P450IA1 and histochemically for ALDH (benzaldehyde and hexanal), DT-diaphorase, gamma-GT and uridine diphosphoglucuronyl dehydrogenase (UDPGdH). In tumor tissues, the largest biochemical changes were found with benzaldehyde dehydrogenase, where activity increased from undetectable levels to 7.4 nmol/min/mg protein, and gamma-GT, where activity increased 12-fold over controls. Increases in other enzymes ranged from 1.26 to 2.84 times that of control liver, except EROD, which decreased, and cEH and mEH, which were unchanged. Histochemical analyses showed the induction of ALDH, gamma-GT, DT-diaphorase and UDPGdH, and the depression of cytochrome P450IA1 in hepatic neoplasms. In addition, marker enzyme histochemistry of neoplasms revealed heterogeneous populations of hepatocytes and absence of necrotic areas.
Carcinogenesis 1993 Feb
PMID:Biochemical and histochemical properties of hepatic tumors of rainbow trout, Oncorhynchus mykiss. 809 46

The relationship between atypical proliferation and carcinogenesis of colonic mucous membrane glands induced by different doses of 1,2-dimethylhydrazine (DMH) was studied by use of histopathological methods and sequential endoscopic observation. The results showed a significant increase of atypical glands in the flat mucosa with the increase in number of DMH injections, the degree of atypical proliferation becoming more serious with the increase of glandular ducts. The following changes were observed under sequential endoscopy: small elevations were first seen on the flat mucosa, then in sequence-flat elevations, hemisphere elevations, substem elevations and finally, stemmed elevations. At the same time, changes such as rubifaction, erosion, central depression and hemorrhage on the tumor surface were frequently encountered. It is concluded that atypical glandular proliferation in the flat mucosa of the colon is a precancerous lesion of colonic carcinoma.
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PMID:[A histogenetic study on the carcinogenesis of colonic mucous membrane glands induced by 1,2-dimethylhydrazine in rats]. 816 80

The present studies examined the impact of a processed garlic powder on the in vivo occurrence of DNA adducts caused by N-nitroso compounds (NOC) in rats. Addition of 2% garlic powder to diets containing aminopyrine and sodium nitrite (each at 600 mg/kg) reduced the occurrence of both 7-N-methyldeoxyguanosine (7-N-mG) and 6-O-methyldeoxyguanosine (6-O-mG) adducts to rat liver DNA by approximately 55%; and over 80% when 4% garlic was provided. Dietary supplementation with garlic powder (2 and 4%) also reduced the occurrence of 7-N-mG and 6-O-mG adducts by approximately 40 and 60% respectively, in rats intubated with N-nitrosodimethylamine (150 mg/kg body wt). The quantity of 7-N-mG and 6-O-mG adducts in mammary tissue of rats given intravenous N-methyl-N-nitrosourea (50 mg/kg body wt) was reduced over 50% in rats fed 2% garlic compared to controls. The depression in the occurrence of these adducts was approximately 70% when dietary garlic was increased to 4%. These experiments suggest the reduction in DNA adducts caused by processed garlic powder likely reflects a depression in the formation of NOC from precursors and changes in the bioactivation and/or denitrosation of NOC.
Carcinogenesis 1994 Feb
PMID:Dietary garlic suppresses DNA adducts caused by N-nitroso compounds. 831 28

The present studies assessed the impact of various sources of garlic and their constituents (water- and ethanol-extracts and S-allylcysteine) on the in vivo binding of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) to rat mammary cell DNA. The provision of dietary raw garlic powder (2%) or its water-extract (1.5%) reduced DMBA-DNA binding by 33 and 46% respectively. Dietary supplementation with a commercially available deodorized garlic powder (powder A) at 2 or 4% depressed the occurrence of adducts by 50 and 78% respectively, while providing a commercially available high sulfur garlic preparation (powder B) at 2% reduced binding by 56%. A pair-feeding study revealed that the depression in carcinogen binding was independent of food intake or weight gain. Although 1% raw garlic powder did not significantly influence the occurrence of DMBA-DNA adducts, an equivalent as the water-extract (0.75%), the ethanol-extract (0.015%) or commercially available powders (A and B) reduced DMBA adducts in mammary tissue by 44, 25, 71 and 65% respectively. Dietary fortification with S-allylcysteine (SAC), a water-soluble constituent of processed garlic, caused a progressive decrease in the binding of DMBA to DNA. Studies with SAC suggest the primary effect of garlic and its constituents is on the bioactivation and binding of the carcinogen rather than DNA repair. These data reveal that several forms of garlic are effective, although variable, in altering carcinogen bioactivation and presumably chemically induced carcinogenesis.
Carcinogenesis 1993 Aug
PMID:Impact of various sources of garlic and their constituents on 7,12-dimethylbenz[a]anthracene binding to mammary cell DNA. 835 46

Rats (Wistar, female, 4 weeks old) were fed iron-deficient (Fe-; 2.2 micrograms Fe/g) or manganese- and copper-deficient (Mn.Cu-; 0.3 microgram Mn/g, 0.4 microgram Cu/g) diets for 8 weeks to determine the oxidative damage of DNA by element deficiency. After feeding of the diets, 2-nitropropane (2-NP, 80 mg/kg body weight) was administered i.p. as an inducer of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) to the element-deficient rats. The hemoglobin concentration of rats in the Fe- group showed an induction of severe anemia (8.4 g/100 ml whole blood). In the Mn.Cu- group, Mn-superoxide dismutase (SOD) activities of plasma and Cu.Zn-SOD activities were significantly lower than that of the normal diet group. However, total SOD activities of plasma were not depressed severely in contrast to that of the liver in the Mn.Cu- group. Background (spontaneous) levels of 8-OH-dG in normal diet group were 0.96 +/- 0.37/10(5) deoxyguanosine (dG), however, significantly higher levels were detected in the Fe- group (1.56 +/- 0.19, P < 0.01). Conversely, a lower (but not significant) level of 8-OH-dG than the normal diet group were detected in the Mn.Cu- group (0.78 +/- 0.08). Six hours after 2-NP treatment, 8-OH-dG levels in liver DNA were significantly induced to 1.44 +/- 0.24 in the normal diet fed group 1.89 +/- 0.22 in the Fe- and 1.08 +/- 0.12 in the Mn.Cu- groups. Compared to the normal diet group, these induced levels of 8-OH-dG in the Fe- group were significantly higher (P < 0.05), and that in Mn.Cu- group were significantly lower (P < 0.05). The high level of 8-OH-dG in severe iron deficiency might be the results of: (i) an increase of hydroxyl radical generation by accumulated copper in hepatocytes; or (ii), a depression of enzymatic activity for removing 8-hydroxy-2'-deoxyguanosine in DNA, which is dependent on divalent cations. On the other hand, the low level of 8-OH-dG in manganese and copper deficiency might be the result of a decrease of lipid peroxidation which has been suggested to be an intermediator from active oxygen species to hydroxyl radical.
Carcinogenesis 1993 Feb
PMID:Spontaneous and 2-nitropropane induced levels of 8-hydroxy-2'-deoxyguanosine in liver DNA of rats fed iron-deficient or manganese- and copper-deficient diets. 838 15

We investigated the expression of the cytochrome P450 isozyme, CYP1A1, during the course of tumor development and examined the distribution of the CYP1A1 protein in hyperplastic foci, adenomas and carcinomas. The expression of NADPH-cytochrome P450 reductase, a flavoprotein that mediates the reduction of cytochrome P450, was also determined. Mice were administered urethane (1 mg/g body wt) and were killed at 10, 22 and 52 weeks to coincide with the time at which hyperplastic foci, adenomas and carcinomas were established, respectively. Protein immunoblotting revealed that the antibody for CYP1A1 detected a protein band of approximately M(r) 56,000 in microsomes from mice treated with beta-naphthoflavone. The antibody for NADPH-cytochrome P450 reductase detected a protein band of approximately M(r) 79,000 in microsomes from control mice and mice treated with beta-naphthoflavone. Immunohistochemical studies showed that CYP1A1 was not detected constitutively in the lungs of both non-tumor- and tumor-bearing mice. Treatment with beta-naphthoflavone evoked high induction of CYP1A1 in morphologically normal tissues of all mice, with localization of the protein mainly in endothelial and alveolar type II cells. In contrast, inducibility of CYP1A1 by beta-naphthoflavone was markedly reduced in early hyperplastic foci seen 10 weeks after urethane exposure. At 22 weeks, CYP1A1 was found at low levels in both solid and papillary tumors, whereas at 52 weeks, lung carcinomas were devoid of expression of this protein. However, CYP1A1 inducibility was highly expressed in late hyperplastic foci manifested at 52 weeks. NADPH-cytochrome P450 reductase was expressed in morphologically normal lung tissue of all mice under control conditions and after treatment with beta-naphthoflavone, and was localized mainly in Clara and alveolar type II cells. In contrast, reductase expression in all tumor sites was diminished and closely paralleled that of CYP1A1. These results demonstrated progressive depression of induced CYP1A1 and reductase expression in early hyperplasias, adenomas and carcinomas, suggesting that the co-ordinate regulation of both enzymes is highly conserved during tumor development. Furthermore, these findings suggested diminished capabilities for metabolic activation of potential toxicants and/or carcinogens after neoplastic transformation.
Carcinogenesis 1996 Jan
PMID:Alterations in expression of CYP1A1 and NADPH-cytochrome P450 reductase during lung tumor development in SWR/J mice. 856 21

There is growing public concern about the possible health risks, particularly increased cancer risks of exposure to magnetic fields (MF) associated with power distribution systems. Recently, we have started a series of animal studies to investigate this issue, using the DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer in female rats. In the present study, female rats were chronically exposed to a 50-Hz, 50 microTesla (microT) MF with or without DMBA treatment. Because alterations in circulating levels of the pineal hormone melatonin and impaired immune system functions have been involved in breast cancer growth, and both melatonin and immune system are thought to be targets for MF-effects, serum melatonin and the proliferative capacity of splenic lymphocytes were determined in MF-exposed and sham-exposed rats. For this purpose, 216 female Sprague-Dawley rats were divided into four groups. Two of the groups (with 99 animals each) received oral applications of DMBA and were either sham-exposed or exposed in a 50-Hz, 50 microT MF for 24 h/day 7 days/week for a period of 91 days. The other two groups (9 animals each) were either sham-exposed or MF-exposed without DMBA treatment. The exposure chambers and all other environmental factors were identical for MF-exposed and sham-exposed animals. The DMBA-treated animals were palpated once weekly to assess the development of mammary tumors. At the end of the three-month period of MF exposure, the number and size of mammary tumors was determined by autopsy. In controls, DMBA induced tumors in approximately 55% of the animals within the 3 month period of sham-exposure. Already 8 weeks after DMBA application, the MF-exposed group exhibited significantly more tumors than sham-exposed animals. At time of autopsy, significantly more MF-exposed DMBA-treated rats exhibited macroscopically visible mammary tumors than DMBA-treated controls, thus indicating that MF exposure enhances the development and growth of cancers in this model. Comparison of the data from 50 microT with recent data from other flux densities indicated that long-term MF exposure of DMBA-treated rats increases the incidence of palpable and/or macroscopically visible mammary tumors in a highly dose-related fashion. Determination of nocturnal serum melatonin after 9 and 12 weeks of exposure at 50 microT did not yield significant differences between MF-exposed rats and sham-exposed controls, whereas a marked suppression of T cell proliferative capacity was seen in MF exposed rats. The data add further evidence to the hypothesis that hormone-dependent tissues such as breast might be particularly sensitive to MF-effects and indicate that immune system depression is involved in the increased breast cancer growth observed in MF exposed rats.
Carcinogenesis 1996 May
PMID:Exposure of DMBA-treated female rats in a 50-Hz, 50 microTesla magnetic field: effects on mammary tumor growth, melatonin levels, and T lymphocyte activation. 864 Sep 36

Reduction of circulating melatonin levels by pinealectomy or constant light has previously been shown to enhance the development and growth of mammary cancers induced by the polyaromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Since pineal melatonin production can also be disturbed by electromagnetic field exposure, we studied whether there is an association between melatonin depression by magnetic field (MF) exposure and DMBA-induced breast cancer growth in female rats. In the present experiments, 216 female Sprague-Dawley rats were divided into 4 groups. Two of the groups (with 99 animals each) received oral applications of DMBA and were either sham-exposed or exposed in a 50-Hz, 100-mG (10 microT) MF for 24 h/d, 7 d/wk, for a period of 91 d. The other two groups (nine animals each) were either sham-exposed or MF-exposed without DMBA treatment. The exposure chambers and all other environmental factors were identical for MF-exposed and sham-exposed animals. The animals were palpated once weekly to assess the development of mammary tumors. At the end of the exposure period, all animals were sacrificed for autopsy and determination of nocturnal melatonin levels in pineal and serum. In controls, DMBA induced palpable tumors in about 55% of the animals within 3 mo after first application. There was a tendency to an enhanced tumor incidence in MF-exposed rats throughout the period of exposure, which, however, was not statistically significant. At autopsy, 60.6% of the sham-exposed and 66.6% of the MF-exposed rats had developed macroscopically visible mammary tumors. Tumor size and tumor burden were similar in both groups. Compared to the groups without DMBA treatment, DMBA-treated rats had significantly lower nocturnal pineal melatonin levels without difference in terms of MF exposure. MF-exposed rats, however, had significantly lower nocturnal melatonin levels in serum than sham-exposed animals. The data demonstrate that although exposure of female rats to a 50-Hz, 100-mG MF significantly decreases circulating melatonin, this is not associated with a significant effect on development or growth of DMBA-induced mammary tumors. In view of the fact that, by using the same model, we recently demonstrated a tumor-copromoting effect of MF exposure at a 10 times higher flux density, the effects of MF exposure on DMBA-induced mammary carcinogenesis appear to be dose dependent.
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PMID:Study on pineal function and DMBA-induced breast cancer formation in rats during exposure to a 100-mG, 50 Hz magnetic field. 864 24

Polychlorinated dibenzo-p-dioxins (PCDDs), commonly known as dioxins, form as unwanted impurities in the manufacturing of chlorophenol and its derivatives--pulp and paper--and in the combustion of municipal, sewage-sludge, hospital, and hazardous waste. Combustion, in presence of a chlorine donor, seems to be a major source of these compounds. High levels of dioxins are also emitted from metallurgical industries including copper smelters, electric furnaces in steel mills, and wire reclamation incinerators. Trace levels are detectable in emissions from motor vehicles using leaded gasoline or diesel fuel, in forest fires, and in residential wood burning. Extremely persistent and widely distributed in the environment, PCDDs have been detected in all three primary and many secondary media. Releases into the air occur mainly from combustor emissions. Atmospheric dispersion, deposition, and subsequent accumulation in the food chain seem to be the major pathways of exposure to the general population. Residues of these chemicals have been detected in soil, sediment, fish, meat, cow's milk, human adipose tissue, and mothers' milk. In general, these chemicals have high lipophilicity. The elimination half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans is approximately 7-11 years. Very little human toxicity data from exposure to PCDDs are available. Health-effect data obtained from occupational settings in humans are based on exposure to chemicals contaminated with TCDD. It produces a spectrum of toxic effects in animals and is one of the most toxic chemicals known. Most of the toxicity data available on TCDD are from high-dose oral exposures to animals. Very few percutaneous and no inhalation exposure data are available in the literature. There is a wide range of difference in sensitivity to PCDD lethality in animals. The signs and symptoms of poisoning with chemicals contaminated with TCDD in humans are analogous to those observed in animals. Dioxin exposures to humans are associated with increased risk of severe skin lesions such as chloracne and hyperpigmentation, altered liver function and lipid metabolism, general weakness associated with drastic weight loss, changes in activities of various liver enzymes, depression of the immune system, and endocrine- and nervous-system abnormalities. It is a potent teratogenic and fetotoxic chemical in animals. A very potent promoter in rat liver carcinogenesis, TCDD also causes cancers of the liver and other organs in animals. Populations occupationally or accidentally exposed to chemicals contaminated with dioxin have increased incidences of soft-tissue sarcoma and non-Hodgkin's lymphoma. No comprehensive studies have been conducted to determine any health impact to the general population from environmental exposure to PCDDs. This paper presents a brief review of relevant animal and human data for projecting any possible health effects from environmental exposures to PCDDs.
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PMID:Health impact of polychlorinated dibenzo-p-dioxins: a critical review. 951 23

Natural killer (NK) cell activity was evaluated after the initiation and promotion steps in a medium-term multi-organ bioassay for carcinogenesis. NK cell activity was assessed in vitro by Cr51 release assay at the 4th and 30th weeks of the experiment. Male Wistar rats were sequentially initiated with N-diethylnitrosamine (DEN i.p.), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN drinking water), N-methyl-N-nitrosourea (MNU i.p.), dihydroxy-di-N-propylnitrosamine (DHPN drinking water) and N,N'-dimethylhydrazine (DMH s.c.) at subcarcinogenic doses for 4 weeks (DMBDD initiation). One group was evaluated at the 4th week and the other was maintained without any further treatment until the 30th week. Two initiated groups were exposed through the diet to 2-acetylaminofluorene (2-AAF) or phenobarbital (PB), from the 6th until the 30th week. Five additional groups were studied to evaluate the effects of each initiator on NK activity. All groups submitted to initiation only, initiation plus promotion, or promotion only, developed significantly more preneoplastic lesions than the untreated control group. The main target organs for tumor development in the initiated animals were the liver and the colon, irrespective of treatment with 2-AAF or PB. NK cell activity was not affected by exposure to genotoxic carcinogens after initiation, at the 4th week. Treatments only with PB or 2-AAF did not change NK cell activity. However, decreased NK cell activity was registered in the group only initiated with DMBDD and in the group given DMBDD+2-AAF. This late depression of NK cell activity at the 30th week could be related to the production of suppressing molecules by the tumor cells.
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PMID:Natural killer activity in a medium-term multi-organ bioassay for carcinogenesis. 1007 72


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