title: Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis.
abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this is an important first step towards the development 3-D tissue as a screening tool.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. mlambros@westernu.edu
authors.forename: Maria Polikandritou
authors.initials: MP
authors.lastname: Lambros
authors.forename: Cyrus
authors.initials: C
authors.lastname: Parsa
authors.forename: HariChandana
authors.initials: H
authors.lastname: Mulamalla
authors.forename: Robert
authors.initials: R
authors.lastname: Orlando
authors.forename: Bernard
authors.initials: B
authors.lastname: Lau
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Doreen
authors.initials: D
authors.lastname: Pon
authors.forename: Moses
authors.initials: M
authors.lastname: Chow
mesh_terms: D017209:Apoptosis; D005720:Gamma Rays / Q000009:adverse effects*; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D013280:Stomatitis / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D013312:Stress, Physiological / Q000235:genetics*; D046509:Tissue Culture Techniques
chemical_list: D016328:NF-kappa B