Early modification of c-myc, Ha-ras and p53 expressions by chemical carcinogens (DMBA, MNU).
7,12-Dimethylbenz[a]anthracene (DMBA) and N-methyl-N-nitrosourea (MNU) are important environmental carcinogens. Their different biological effects were examined in CBA/Ca H-2(K) haplotype inbred mice on the gene expression of c-myc, Ha-ras and p53 through a 24 hour period. Elevated expression of c-myc and Ha-ras genes was found in the spleen, lung, thymus and lymph nodes 6 and 12 hours after DMBA treatment and in the lung and thymus 3 hours after MNU treatment. In the liver, DMBA induced strong onco/suppressor gene expression as early as 6 hours after the treatment, but MNU increased the p53 gene expression 12 hours after the treatment. The gene expression patterns reflected the different mechanism of the direct acting MNU and metabolically activated DMBA. This phenomenon provides evidence as to the usefulness of detection of onco/supressor key gene expression as early molecular epidemiological biomarkers of carcinogenesis and carcinogenic exposure in animal model, useful in human cancer prevention practice as well.
Budán
Ferenc
F
Department of Public Health, University Medical School of Pécs, H-7643 Pécs, Hungary.
Varjas
Tímea
T
Nowrasteh
Ghodratollah
G
Prantner
Ida
I
Varga
Zsuzsa
Z
Ember
Agoston
A
Cseh
József
J
Gombos
Katalin
K
Pázsit
Emese
E
Gobel
Gyula
G
Bauer
Miklós
M
Gracza
Tünde
T
Arany
István
I
Perjési
Pál
P
Ember
István
I
Kiss
István
I
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000737:chemistry / Q000633:toxicity*; D000477:Alkylating Agents / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008297:Male; D008770:Methylnitrosourea / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008808:Mice, Inbred CBA; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D000477:Alkylating Agents; D002273:Carcinogens; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea; D016283:Proto-Oncogene Proteins p21(ras)