J Mol Hist (2009) 40:177–181 DOI 10.1007/s10735-009-9228-z O R I G I N A L P A P E R A mouse model for oral squamous cell carcinoma Remilio A. L. Schoop Æ Mathieu H. M. Noteborn Æ Robert J. Baatenburg de Jong Received: 1 April 2009 / Accepted: 23 July 2009 / Published online: 14 August 2009 The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Despite recent advances, the prognosis of oral squamous cell carcinoma is still poor. Therapeutic options such as radiotherapy, chemotherapy, surgery and the novel treatment option gene therapy are being investigated in animal models. Diverse models have been studied to induce oral squamous cell carcinomas. The carcinogenic 4-nitroquinoline-1-oxide (4NQO) model has proven to be successful although until now it is unknown at what time point the established tumor is a representative squamous cell carcinoma and has a suitable volume for scientiﬁc treatment. For this end we applied 4NQO 3 times a week during 16 weeks and measured the volume of tumor tissue each week until the end of the experiment at 40 weeks. Concurrent histopathology at different time points up to the end of the experiment revealed that all mice bearing oral tumors were diagnosed with squamous cell carci- noma. Immunohistochemistry with markers cyclin D1 and E-cadherin revealed that the generated mouse oral tumors showed strong similarities with the described immunopa- thology in human oral tumors. The 4NQO model is a R. A. L. Schoop Department of Otolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands e-mail: r.a.l.schoop@lumc.nl M. H. M. Noteborn Leiden Institute of Biological Chemistry, Leiden University, Leiden, The Netherlands R. J. Baatenburg de Jong (&) Department of Otolaryngology and Head and Neck Surgery, Erasmus Medical Center, Rotterdam, The Netherlands e-mail: r.j.baatenburgdejong@erasmusmc.nl R. J. Baatenburg de Jong Dr. Molewaterplein 40, 3000 CA Rotterdam, The Netherlands suitable alternative for preclinical gene therapy experi- ments with primary oral tumors. Future survey of thera- peutic options in the carcinogenic 4NQO model should be conducted around 40 weeks after the start of the treatment. Keywords 4-Nitroquinoline-1-oxide Gene therapy Immunocompetent mice Tumor volume Squamous cell carcinoma of head and neck Introduction Oral cancer accounts for almost 275,000 new cases world- wide each year (Parkin et al. 2005). The main risk factors for developing oral cancer are tobacco smoking and consump- tion of alcohol (Boffetta and Hashibe 2006). Continuation of smoking during treatment can lead to increased morbidity and mortality (Videtic et al. 2003). Primary treatment is associated with high morbidity and function loss of the organ, while up to 50% die due to recurrence (Monnerat et al. 2002). Present-day treatment, surgery, radiotherapy or che- motherapy or a combination of these three, has had not- withstanding the improvements, no signiﬁcant improvement in survival (Cooper et al. 2004). For that reason new treat- ments, such as (targeted) gene therapy are being developed (Ganesh et al. 2008; Ghobrial et al. 2005; Loefﬂer-Ragg et al. 2008; Schoop et al. 2004; 2008). New therapies can be investigated both in vitro and in vivo. The drawback of in vitro laboratory study is the dissimilarity between the cell culture and the physiological processes giving misleading results. Several animal models for oral squamous cell carcinoma are used including hamster, rat and mouse models, with each model having its own advantages and disadvantages. Earlier experiments were set to induce tumors by mechanical damaging the jaw 123