Biomedical subjects

Z Gyöngyi

Publications and source records attributed to Z Gyöngyi.

7 recordsLinked to original sources

PubMed2000

Comparison of early onco/suppressor gene expressions in peripheral leukocytes and potential target organs of rats exposed to the carcinogen 1-nitropyrene.

An in-vivo model has been developed to study early expressions of c-myc, Ha-ras oncogenes and p53 suppressor gene as biomarkers of carcinogenic exposure and/or tumorigenesis. In order to validate the in-vivo expression changes as biomarkers, rats were treated with the outdoor air pollutant carcinogen 1-nitropyrene. The gene expression levels were measured after 24 and 48 h in potential target tissues (lung, liver, lymph nodes, kidneys, spleen) and in peripheral blood leukocytes. Another main objective was to prove the applicability of leukocytes as a surrogate tissue, having a similar expression pattern of the selected genes upon carcinogenic exposure. The c-myc oncogene was not suitable as an early biomarker because of the lack or low level of its expression. However, in the case of the other oncogene Ha-ras and the suppressor gene p53, remarkable and early changes were detected in the expression signals. Similar expression patterns could only be detected in leukocytes and the spleen; therefore we continue this validation study by using other types and routes of exposure.

Animals↗

PubMedDate not supplied

Deuterium depletion can decrease the expression of C-myc Ha-ras and p53 gene in carcinogen-treated mice.

In spite of the fact that the deuterium concentration is over 10 mmol/l in all living organisms, its possible role has been ignored for six decades. Recent studies have shown that the depletion of the naturally occurring deuterium can result in tumour regression in mice, dogs, cats and humans. The effect of deuterium depletion on gene expression plays a key part in tumour development. The carcinogen, 7,12-dimethylbenz(alpha)anthracene (DMBA), was used to increase gene expression in "short term" investigations. The expression of c-myc, Ha-ras and p53 gene was followed in CBA/Ca sensitive inbred mice drinking tap water or deuterium-depleted water (DDW) after induction. By detecting the RNA expression 48 hours after exposure to the carcinogen it was found that the expression of all genes investigated was inhibited in six different organs (spleen, lung, thymus, kidney, liver and lymph node) in the DDW-treated group. It is suggested that genes playing a key role in the cell cycle regulation and tumour development are sensitive to deuterium depletion.

Animals↗

PubMedDate not supplied

1-Nitropyrene induces elevated expression of oncogenes and tumor suppressor genes 24 hours after treatment in CBA/Ca mice.

In an earlier experiment we found that 1-nitropyrene treatment causes an increase in the expression of certain onco/suppressor genes in different organs of CBA/Ca mice. In order to further study the kinetics and significance of these gene expression changes, we determined the effect of 1-nitropyrene treatment on the expression of c-myc, p53, Ha-ras, N-ras, and Ki-ras genes, 24 hours after treatment. Expression of the ras family did not change during the studied interval, while elevated expression of c-myc and p53 genes was observed in the spleen, bone marrow and lymph nodes (only c-myc in the latter). The results suggest a different pattern for the involvement of the ras genes in 1-nitropyrene-caused carcinogenesis, and also underlines the differences in the organ specificity of chemical carcinogens in humans and in experimental animals. In the present study, we also confirmed the in vivo applicability of early gene expression changes as biomarkers of carcinogenic exposure.

Animals↗

PubMedDate not supplied

Effect of E-2-(4'-methoxybenzylidene)-1-benzosuberone on the 7,12-dimethylbenz[alpha]anthracene-induced onco/suppressor gene action in vivo II: A 48-hour experiment.

The cyclic chalcone analogue, E-2-(4'-methoxybenzylidene)-1-benzosuberone (MBB), has been found to show outstanding in vitro cytotoxic activity against P388, L1210, Molt 4/C8 and CEM cells, as well as against a panel of human cell lines. In order to determine whether this promising antineoplastic activity would extend to anticarcinogenic properties, the effect of MBB on the 7,12-dimethylbenz [alpha]anthracene (DMBA)-induced expression of the c-myc, Ha-ras and p53 genes in isolated RNA from the liver, lung, kidney, spleen, thymus, lymph nodes and bone marrow of CBA/Ca inbred mice was investigated. Earlier we had found that administration of MBB can reduce the DMBA-induced 24-hour gene expressions most effectively when it is administered prior to, or simultaneously with, the DMBA-treatment to female CBA/Ca inbred mice. As a continuation of this study, we investigated the effect of MBB on the DMBA-induced gene expressions according to the two protocols in a 48-hour experiment. The 48-hour experiment with female and male CBA/Ca inbred mice also determined the compound which effectively reduced the DMBA-induced c-myc and Ha-ras overexpressions in almost all tissues. While the DMBA-induced gene expressions showed very different patterns, the effectiveness of the two different administrations of MBB was found to be very similar in the two sex groups. At the same time, contrary to the 24-hour experiment, increased p53 gene expression levels could be seen in several tissues in both sex groups. In order to get a better understanding of the effects of MBB on the DMBA-induced gene expressions "long-term" and "follow-up" studies should be performed.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Early effects of different cytostatic protocols for head and neck cancer on oncogene activation in animal experiments.

In vivo investigations on oncogenes and onco-suppressor genes may provide new findings on the potential carcinogenic effects of various cytostatic protocols inducing secondary tumours of the head and neck. Further surgeries are often necessary due to regional recurrence after the Cisplatin-supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol in the treatment of human head and neck tumours. Our earlier studies have illustrated the carcinogenic and mutagenic potential of Cisplatin. The effect of Cisplatin on the alteration of different onco- and suppressor genes has also been proven. Our present study aimed at investigating the early effects of the BVM and the CFu (Cisplatin, 5-Fluorouracil) protocols on early oncogene and tumour suppressor gene expressions in mice. Body weight equivalent amounts of cytostatics were administered intraperitoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes were examined. The protocols caused detectable changes. A "short-term" in vivo test, the 24-hour examination of gene expression, is suitable for detecting early effects of carcinogen exposure. The alterations of gene expression, caused by the Cisplatin-containing protocol, draw attention to the probable role of Cisplatin in the development of regional recurrence and to the possibility of prevention.

Animals↗