Early modification of c-myc, Ha-ras and p53 expressions by N-methyl-N-nitrosourea

Ferenc Budán, Tímea Varjas, Ghodratollah Nowrasteh, Zsuzsa Varga, Imre Boncz, József Cseh, Ida Prantner, Tibold Antal, Emese Pázsit, Gyula Góbel, Miklós Bauer, Tünde Gracza, Pál Perjési, István Ember, Zoltán Gyóngyi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Methylnitrosourea (MNU) is a well-known pluripotent direct-acting carcinogen. Formation of MNU following incubation of various meats with additional nitrite under in vitro acidic conditions is possible. It is possible that many species, including humans, are exposed to carcinogenic MNU, generated in their alimentary tract. Previously, an animal model was developed by our research group to investigate the expression of three genes c-myc, Ha-ras and p53 as early molecular epidemiological biomarkers of carcinogenic exposure or carcinogenesis caused by DMBA (dimethylbenz[a]anthracene). The aim of this study was to investigate the early effect of MNU on the gene expression levels. MNU is a direct-acting carcinogen which spontaneously and rapidly degrades, so any effect on the gene expression is observed in 24 hours. Our results show the maximum effect in vivo on the gene expression at 12 hours after the MNU treatment; on the other hand, 24 hours after the treatment, the elevated gene expressions decreased in target organs (bone marrow, lung, lymph nodes). Our results correspond to "long-term" experiments of the carcinogenic effect of MNU in different target organs. Our findings suggest that MNU has an impact on the expression of c-myc, Ha-ras and p53 genes in 12 hours, especially in bone marrow. Overexpression of these genes occurs as an early biological effect of exposure to chemical carcinogens. According to our results, the high expression of these genes could indicate MNU exposure and these genes could take part in MNU-induced tumorigenesis.

Original languageEnglish
Pages (from-to)793-798
Number of pages6
JournalIn Vivo
Volume22
Issue number6
Publication statusPublished - Nov 1 2008

Keywords

  • Carcinogenesis
  • DMBA
  • Gene expression
  • Ha-ras
  • MNU
  • Mice
  • c-myc
  • p53
  • ras

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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  • Cite this

    Budán, F., Varjas, T., Nowrasteh, G., Varga, Z., Boncz, I., Cseh, J., Prantner, I., Antal, T., Pázsit, E., Góbel, G., Bauer, M., Gracza, T., Perjési, P., Ember, I., & Gyóngyi, Z. (2008). Early modification of c-myc, Ha-ras and p53 expressions by N-methyl-N-nitrosourea. In Vivo, 22(6), 793-798.