Early modification of c-myc, Ha-ras and p53 expressions by N-methyl-N-nitrosourea.
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[alpha]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.
Budán
Ferenc
F
Department of Public Health, Mihály Pekár Medical and Life Science Library.
Varjas
Tímea
T
Nowrasteh
Ghodratollah
G
Varga
Zsuzsa
Z
Boncz
Imre
I
Cseh
József
J
Prantner
Ida
I
Antal
Tibold
T
Pázsit
Emese
E
Gobel
Gyula
G
Bauer
Miklós
M
Gracza
Tünde
T
Perjési
Pál
P
Ember
István
I
Gyöngyi
Zoltán
Z
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects*; D011905:Genes, ras / Q000187:drug effects*; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D009928:Organ Specificity; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics
D002273:Carcinogens; D012333:RNA, Messenger; D008770:Methylnitrosourea