title: Carcinogenesis of the Oral Cavity: Environmental Causes and Potential Prevention by Black Raspberry.
abstract: Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical. Better understanding of the mechanisms of oral carcinogenesis can assist in the development of novel biomarkers for early detection and strategies for disease prevention. Toward this goal, several animal models for carcinogenesis in the oral cavity have been developed. Among these are xenograft, and transgenic animal models, and others employing the synthetic carcinogens such as 7,12-dimethylbenz[a]anthracene in hamster cheek pouch and 4-nitroquinoline-N-oxide in rats and mice. Additional animal models employing environmental carcinogens such as benzo[a]pyrene and N'-nitrosonornicotine have been reported. Each model has certain advantages and disadvantages. Models that (1) utilize environmental carcinogens, (2) reflect tumor heterogeneity, and (3) accurately represent the cellular and molecular changes involved in the initiation and progression of oral cancer in humans could provide a realistic platform. To achieve this goal, we introduced a novel nonsurgical mouse model to study oral carcinogenesis induced by dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and tobacco smoke constituent, and its diol epoxide metabolite (±)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene [(±)-anti-DB[a,l]PDE]. On the basis of a detailed comparison of oral cancer induced by DB[a,l]P with that induced by the other above-mentioned oral carcinogens with respect to dose, duration, species and strain, cellular and molecular targets, and relative carcinogenic potency, our animal model may offer a more realistic platform to study oral carcinogenesis. In this perspective, we also discuss our preclinical studies to demonstrate the potential of black raspberry extracts on the prevention of OSCC. Specifically, we were the first to demonstrate that black raspberry inhibited DB[a,l]P-DNA binding and of particular importance its capacity to enhance the repair of DB[a,l]P-induced bulky lesions in DNA. We believe that the information presented in this perspective will stimulate further research on the impact of environmental carcinogens in the development of oral cancer and may lead to novel strategies toward the control and prevention of this disease.
authors.forename: Karam
authors.identifier: 0000-0002-4198-0696
authors.initials: K
authors.lastname: El-Bayoumy
authors.forename: Kun-Ming
authors.initials: KM
authors.lastname: Chen
authors.affiliation: Department of Pathology, Yale University, Yale School of Medicine , New Haven, Connecticut 06510, United States.
authors.forename: Shang-Min
authors.initials: SM
authors.lastname: Zhang
authors.forename: Yuan-Wan
authors.initials: YW
authors.lastname: Sun
authors.forename: Shantu
authors.initials: S
authors.lastname: Amin
authors.affiliation: Department of Medicine, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
authors.forename: Gary
authors.initials: G
authors.lastname: Stoner
authors.affiliation: Department of Basic Science, and Department of Environmental Medicine, New York University College of Dentistry and New York University School of Medicine , New York, New York 10010, United States.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Guttenplan
mesh_terms: D065767:Activation, Metabolic; D000818:Animals; D063646:Carcinogenesis; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D018736:DNA Adducts; D004260:DNA Repair; D004195:Disease Models, Animal; D006801:Humans; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D009154:Mutation; D010936:Plant Extracts / Q000494:pharmacology*; D065856:Rubus; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53