In vivo effects of afobazole (2-mercaptobenzimidazole derivative) on the 7,12-dimethylbenz [alpha]anthracene-induced oncogene and suppressor gene expression.
BACKGROUND
Afobazole, a new 2-mercapto-benzimidazole derivative, exhibited antimutagenic activity in chromosome aberration tests and antioxidant properties. The aim of this study was to demonstrate the potential chemopreventive effect of afobazole on the level of early biological effects by analysing changes in oncogene and tumor suppressor gene expression.


METHODS
Single intraperitoneal (i.p.) treatment with 7,12-dimethylbenz[alpha]anthracene (DMBA) combined with afobazole was administered to CBA/Ca (sensitive H-2K haplotype) female mice. The expression of Ha-ras and p53 was determined in the vital organs (liver, spleen, lung, kidney, thymus, lymph nodes and bone marrow) 24, 48 and 72 hours later.


RESULTS
Coadministration of afobazole and DMBA resulted in a decrease of DMBA-induced overexpression of Ha-ras and p53. Reduction of the DMBA-induced gene expression was most striking when afobazole was given in parallel with DMBA.


CONCLUSIONS
Our results strengthen the previous assumption, which was based on in vitro results, that afobazole has a chemopreventive effect in vivo.
Szanyi
István
I
Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, University of Pécs, Munkdcsy u. 2, H-7621 Pécs, Hungary. istvan.szanyi@aok.pte.hu
Lujber
László
L
Gerlinger
Imre
I
Pytel
József
J
Bauer
Miklós
M
Csejtey
András
A
Szele
Eszter
E
Gombos
Katalin
K
Kiss
István
I
Seredenin
Sergey
S
Yarkova
Milada
M
Ember
István
I
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016147:Genes, Tumor Suppressor; D051379:Mice; D008808:Mice, Inbred CBA; D009025:Morpholines / Q000494:pharmacology*; D009857:Oncogenes
C410924:2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole; D001562:Benzimidazoles; D009025:Morpholines; D015127:9,10-Dimethyl-1,2-benzanthracene