11 Original studies/Studi originali General topics/Argomenti generali Eur. J. Oncol., vol. 17, n. 1, pp. 11-21, 2012 Kinase inhibitors reduce 7,12-dimethylbenz[a]anthracene-induced onco- suppressor gene expression in short-term experiments Inibitori delle chinasi riducono l’espressione genica dell’onco-soppressore indotto da 7,12- dimethylbenz[a]anthracene in esperimenti a breve termine Péter Gergely*, Ferenc Budán**, István Szabó**, Géza Mezey***, Árpád Németh**, András Huszár**, János Iványi****, Katalin Gombos**, Ádám Knapp*****, László Őrfi******, György Kéri*******, István Ember** * Institute of Forensic Medicine, University of Debrecen, Debrecen, Hungary **DepartmentofPublicHealth,UnivesityofPécsMedicalSchool,Pécs,Hungary *** Department of Neurosurgery, University of Debrecen, Debrecen, Hungary **** Department of Hematology, Markusovszky Hospital, Szombathely, Hungary ***** Hegyvidék Publishing, Budapest, Hungary ****** Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary ******* Pathobiochemistry Research Group of the Hungarian Academy of Sciences, Department of Medical Chemistry, Budapest, Hungary Received/Pervenuto 24.11.2011 - Accepted/Accettato 25.1.2012 Address/Indirizzo:IstvánSzabóDepartmentofPublicHealth,UniversityofPécsMedicalSchool,Szigetistr12,H-7624Pécs,Hungary E-mail: bokor28@yahoo.co.uk Summary 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 previ- ously observed. The potential antineoplastic and chemopreventive properties of four protein tyro- sine kinase (PTK) inhibitor molecules were studied. Materials and methods. In order to deter- mine 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) simultane- Riassunto Finalità. È stato precedentemente osservato che il trattamento con 7,12- dimethylbenz[a] anthracene(DMBA)inducel’espressionedionco- geni e di geni onco-soppressori, che costituiscono indicatori precoci di carcinogenesi. Il presente studio valuta le potenziali proprietà antineopla- stiche e chemiopreventive di quattro inibitori del- le proteine tirosin-chinasi (PTK). Materiali e me- todi. Per determinare se una potenziale attività antineoplastica di queste molecole sia associata a proprietà anticarcinogeniche, è stato valutato il loro effetto sull’espressione dei geni onco-sop- pressori Ha-ras e p53, indotta dal DMBA, nel fe- gato, polmoni, midollo osseo e rene di topi di cep- poCBA/Ca.Lemolecoleinesamesonostatesom- ministrate(I)24oreprima,(II)durante,o(III)24