Genetic instability and oral cancer
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 papilloma...
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Pontificia Universidad Católica de Valparaíso
2000
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oai:scielo:S0717-345820000001000052003-08-18Genetic instability and oral cancerPark,No-HeeKang,Mo K. 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. <A NAME="Article"></A>info:eu-repo/semantics/openAccessPontificia Universidad Católica de ValparaísoElectronic Journal of Biotechnology v.3 n.1 20002000-04-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582000000100005en |
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Scielo Chile |
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Scielo Chile |
| language |
English |
| description |
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. <A NAME="Article"></A> |
| author |
Park,No-Hee Kang,Mo K. |
| spellingShingle |
Park,No-Hee Kang,Mo K. Genetic instability and oral cancer |
| author_facet |
Park,No-Hee Kang,Mo K. |
| author_sort |
Park,No-Hee |
| title |
Genetic instability and oral cancer |
| title_short |
Genetic instability and oral cancer |
| title_full |
Genetic instability and oral cancer |
| title_fullStr |
Genetic instability and oral cancer |
| title_full_unstemmed |
Genetic instability and oral cancer |
| title_sort |
genetic instability and oral cancer |
| publisher |
Pontificia Universidad Católica de Valparaíso |
| publishDate |
2000 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582000000100005 |
| work_keys_str_mv |
AT parknohee geneticinstabilityandoralcancer AT kangmok geneticinstabilityandoralcancer |
| _version_ |
1718441688042569728 |