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C Varga

Publications and source records attributed to C Varga.

42 records · Page 3Linked to original sources

Changes in expression of onco- and suppressor genes in peripheral leukocytes--as potential biomarkers of chemical carcinogenesis.

An animal model was developed to investigate the expression of two oncogenes (c-myc, Ha-ras) and a suppressor gene (p53) as early markers of the effects of carcinogenic exposure and/or tumourigenesis. Inbred Long-Evans rats were treated with 7,12-dimethylbenz(a)anthracene and the transient/permanent gene expressions were measured after 24 and 48 hours by dot blotting in potential target tissues (lung, liver, lymph nodes, kidneys, spleen) and in peripheral blood leukocytes. The aim of the study was to test blood leukocytes, as surrogate tissue, showed similar expression patterns of the selected genes following carcinogenic exposure. c-myc did not prove to be an applicable early biomarker due to the lack of or low level of its expression. However, remarkable of early elevations were detected in the expression signals of Ha-ras and p53.

9,10-Dimethyl-1,2-benzanthracene↗

Long-term effects of 1-nitropyrene on oncogene and tumor suppressor gene expression.

Late changes in the expression of oncogenes and tumor suppressor genes following carcinogenic exposure were examined in lung, liver and kidney. 1-Nitropyrene (1-NP), which is a high-risk exposure factor in urban and industrial zones, was used as a carcinogenic agent. c-myc, Ha-ras and p53 gene expression was investigated after administration of a single dose of 1-NP to sensitive CBA/Ca mice in lung, liver and kidney for one year. One week after a single dose 1-NP administration, the expression of p53 was elevated in the liver, but, decreased in the lung and kidney. There was no increase in the expression of c-myc or Ha-ras genes at that time. One month after the administration of the 1-NP, the expression of p53 was increased in the kidney while the expression of Ha-ras and p53 was elevated in the liver. There was no significant difference in gene expression between the treated and control animal groups at any of the investigated periods except for the above-mentioned organs and at the end point of the investigation. According to the literature, 1-NP and its metabolites remain at high concentrations in the kidney, liver and lung. The concentration of the carcinogenic agent and the expression of the studied genes did not seem to correlate with each other in this experiment.

Animals↗

Carcinogenic effects of cytostatic protocols in CBA/Ca mice.

An in vivo mouse model was developed in order to study the characteristics of secondary tumor induction by cytostatic drug combinations used in human anticancer treatment. In this model we have proved the carcino-leukemogenic effects of widely used chemotherapeutical drug combinations (CHOP, COPP, COPBLAM, VAM). The carcinogenic hazards of cyclophosphamide and other alkylating drugs could also be demonstrated in our model.

Animals↗

Effect of different cytostatic protocols on oncogene expression in CBA/Ca mice.

In vivo investigations on oncogene action may provide new findings on the toxicology of potential carcinogens. In this study we investigated the early effects of different cytostatic protocols on early oncogene expression in CBA/Ca mice. Most of the examined protocols showed detectable early changes, especially those containing cyclophosphamide. The most frequently involved oncogenes were N-ras, c-myc, and c-myb.

Animals↗

Studies on genotoxicity of orally administered crocidolite asbestos in rats: implications for ingested asbestos induced carcinogenesis.

The early genotoxic action of oral exposure to UICC crocidolite asbestos fibres was studied in different short-term tests. Fischer-344 rats were gavaged with 50 mg/b.w.kg untreated asbestos fibres and fibres which had been allowed to adsorb benzo(a)pyrene molecules from extremely low concentration (0.25-2.5 microg/ml) aqueous solutions. This system can be considered a model for the drinking of potable water contaminated by asbestos fibres together with biologically active organic micro-pollutants. The Ames Salmonella mutagenicity assay was performed on concentrated urine and serum samples of treated animals. The formation of micronuclei and sister chromatid exchanges was also studied in the bone marrow of the exposed rats. The micronucleus analysis indicated marginal genotoxic activity only upon treatment with crocidolite prepared from the solution of 1 microg/ml. A dose-dependent increase was, however, demonstrated in the sister chromatid exchange frequency upon treatment with benzo(a)pyrene coated fibres. These experiments suggest the acute cogenotoxic activity of such fibres in orally exposed animals.

Administration, Oral↗

Oxidative stress in experimental diabetes induced by streptozotocin.

It is known that streptozotocin (STZ) penetrating into the organism generates nitrogen monoxide (NO). Therefore, it is justified to presume, that in beta-cell destruction thereby induced, peroxinitrit resulting from NO and superoxide (O2-) reaction has an important role. It has also been studied how pro- and antioxidant systems change in STZ induced experimental diabetes in rat organs. Beside pro- and antioxidant systems of plasma and red blood cell hemolysates, changes in homogenates of the following organs were studied: liver, kidney, heart, lungs, spleen, brain, muscles and pancreas. We tested and compared antioxidant enzymes (superoxide dismutase-, glutathione peroxidase- and catalase activities) glutathione reductase activity regenerate reduced glutathione (GSH). The oxidized, reduced glutathione values and lipid peroxidation changes were measured. From our studies it has appeared that STZ treatment generally induces an oxidative predominance in tissues. Changes in this model thereby, can be compared to changes occurring in type 1 human diabetic patients.

Animals↗