Aims. Elevated expression of oncogenes and tumour suppressor genes after treatment with 7,12- dimethylbenz[a]anthracene (DMBA) as early markers of carcinogenesis has been previously observed. The potential antineoplastic and chemopreventive properties of four protein tyrosine kinase (PTK) inhibitor molecules were studied. Materials and methods. In order to determine whether a promising antineoplastic activity would extend to anticarcinogenic properties, the effects of these molecules on the 7,12 DMBA-induced expression of Ha-ras oncogene and p53 tumour suppressor genes in the liver, lungs, bone marrow and kidney of CBA/Ca inbred mice was investigated. The experimental molecules were administered (I) 24 hours prior to, (II) simultaneously with, or (III) 24 hours after DMBA exposure. Results. PTK inhibitor (1Z)-1-(3,4-Dihy-droxybenzylidene)-3,4-dihydro[1,4]oxazino[3,4-b]quinazolon-6(1H)-on and N-(3-bromophenyl)-6,7-dimethoxy quinazolin-4-amine reduced the expression of Ha-ras and p53 genes in all of the examined organs in the different treated groups. Another two PTK inhibitor, 2-Benzyl-1-(4-hydroxyphenyl)-3-me-thyl-2,3-dihydroimi-dazo[5,1-b]quinazolin-9(1H)-one and 2-[(2E)-2-(3,4-dihydroxybenzylidene)hydrazino]-N-(3-nitrophenyl)-2-oxoacetamide reduced both Haras and p53 gene expression induced by DMBA in all of the examined organs (except for the kidneys, where only Ha-ras expression decreased) in all of the experimental settings. Conclusions. Our in vivo short-term experimental results provide some evidence, that PTK inhibitors exhibit antineoplastic and chemopre-ventive effects by reversing the overexpression of the early markers of carcinogenesis. This early molecular biomarker model indicates the first steps of malignant transformation at subcellular level and possible anti-tumour effects, as well.
|Translated title of the contribution||Kinase inhibitors reduce 7,12-dimethylbenz[a]anthracene-induced oncosuppressor gene expression in short-term experiments|
|Number of pages||11|
|Journal||European Journal of Oncology|
|Publication status||Published - Dec 1 2012|
- Gene expression
- Tyrosine-kinase inhibitor
ASJC Scopus subject areas