Genetic instability and oral cancer



Document title: Genetic instability and oral cancer
Journal: Electronic journal of biotechnology
Database: PERIÓDICA
System number: 000267140
ISSN: 0717-3458
Authors: 1
Institutions: 1University of California, School of Dentistry, Los Angeles, California. Estados Unidos de América
Year:
Season: Abr
Volumen: 3
Number: 1
Country: Chile
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English abstract Development of oral cancer proceeds through discrete molecular genetic changes that are acquired from the loss of genomic integrity after continued exposure to environmental risk factors. Of particular importance in oral cancer development are tobacco-related chemical carcinogens and human papillomavirus (HPV) infection. To understand the mechanisms by which these risk factors contribute to tumorigenesis, we developed an in vitro model of sequential, multistep oral carcinogenesis model of normal human oral keratinocytes (NHOK) by immortalizing these cells with cloned "high risk" HPV genome. HPV viral genome alone failed to give rise to a tumorigenic cell population, which required further exposure to chemical carcinogens. HPV-immortalized cells exhibited impaired cell cycle control and DNA repair activity upon exposure to DNA damaging agents, and accumulated elevated frequency of spontaneous and mutagen-induced mutation. Furthermore, expression of E6 and E7 oncoproteins of "high risk" HPV were found to be sufficient for the enhanced mutation frequency in NHOK. These findings suggest that viral infection in combination with existing chemical carcinogens may be the paramount causative agents for the induction of genetic instability and development of oral cancer
Disciplines: Medicina,
Biología
Keyword: Odontología,
Oncología,
Virus,
Cáncer,
Boca,
Papiloma,
Queratinocitos,
Factores de riesgo,
Genoma
Keyword: Medicine,
Biology,
Dentistry,
Oncology,
Virus,
Cancer,
Mouth,
Papillomavirus,
Keratinocytes,
Risk factors,
Genome
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