• 6/28/2004
  • A Z Reznick1, O Hershkovich1,2 and R M Nagler1,2
  • British Journal of Cancer

Oropharyngeal cancer, which is usually squamous cell carcinoma, is the most common head and neck malignancy and accounts for 2-4% of all new cancers. It is primarily induced by exposure to tobacco. The paradigm of cigarette smoke induced oropharyngeal cancer’s pathogenesis is based on the assumption that a constant direct attack of various cigarette smoke carcinogens causes widespread accumulating cellular and DNA aberrations in the oropharyngeal mucosal cells, in turn eventually resulting in malignant transformation. However, there is never a direct contact between cigarette smoke and the oropharyngeal mucosa. Saliva, bathing the mucosa from the oral cavity to the larynx, always intervenes, and cigarette smoke must first interact with saliva before it reaches the mucosa. The current study investigated the role of saliva in the pathogenesis of oropharyngeal cancer. A synergistic effect of cigarette smoke and saliva on oral cancer cells was demonstrated. This synergism is based on the reaction between redox active metals in saliva and low reactive free radicals in cigarette smoke, which results in the production of highly active hydroxyl free radicals. Thus, when exposed to cigarette smoke, salivary behavior is reversed, and the saliva loses its antioxidant capacity and becomes a potent prooxidant milieu. The devastating role of cigarette smoke-borne aldehydes was demonstrated as well. Based on these results and on our recent reports demonstrating that cigarette smoke destroys various salivary components, including protective ones such as peroxidase, the most important salivary antioxidant enzyme, a comprehensive view of the pivotal role of saliva in the pathogenesis of cigarette smoke-induced oropharyngeal cancer is suggested.

1Department of Oral and Maxillofacial Surgery, Oral Biochemistry Laboratory and Salivary Clinic, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
2Department of Anatomy and Cell Biology, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

Correspondence to: Dr RM Nagler, E-mail: nagler@tx.technion.ac.il
Received 5 September 2003; revised 22 January 2004; accepted 3 March 2004; published online 25 May 2004

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