Normal human oral keratinocytes are more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine-induced cytotoxicity and apoptosis than HPV-immortalized oral keratinocytes

  • Authors:
    • J Baek
    • C Bertolami
    • B Bonavida
    • N Park
  • View Affiliations

  • Published online on: January 1, 1997     https://doi.org/10.3892/ijo.10.1.47
  • Pages: 47-51
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Exposure of HPV-immortalized, but not normal human oral keratinocytes, to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) renders the cells tumorigenic. The underlying mechanism of this differential response of normal and immortalized cells was investigated. Normal primary human oral keratinocytes and three HPV-immortalized human oral keratinocyte cell lines exposed to MNNG were evaluated for survival rate, single and double-strand DNA breaks, and the expression of p53 and bcl-2 proteins. MNNG exposure for 2 h induced both greater cytotoxicity and a more rapid kinetic of cell death in normal keratinocytes than in the immortalized cells. Further, normal keratinocytes were more sensitive to lower concentrations of MNNG that were subtoxic for the immortalized cells. Likewise, with lower concentration of MNNG (50 mu M), significant single-strand DNA breaks in normal keratinocytes were induced whereas no such effect was seen in the immortalized cells. Double-strand DNA fragmentation (apoptosis) was observed in normal keratinocytes exposed to 50 mu M MNNG but not in the immortalized cells. Higher concentrations of MNNG (100 mu M) were toxic to both normal and immortalized cells although the normal cells were still more sensitive and with faster kinetics of cell death. MNNG-induced apoptosis was not attributable to down regulation of the anti-apoptotic product bcl-2 in normal cells; however, exposure of normal keratinocytes to MNNG did result in induction of the apoptotic gene p53. No change in p53 level was seen in the immortalized cells. These findings suggest that the selective sensitivity of normal keratinocytes to MNNG-induced apoptosis is in part due to the induction of p53. The HPV-immortalized cells are resistant to MNNG-induced apoptosis and therefore are capable of undergoing mutations affecting cell proliferation and resulting in tumori-genicity.

Related Articles

Journal Cover

January 1997
Volume 10 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Baek J, Bertolami C, Bonavida B and Park N: Normal human oral keratinocytes are more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine-induced cytotoxicity and apoptosis than HPV-immortalized oral keratinocytes. Int J Oncol 10: 47-51, 1997
APA
Baek, J., Bertolami, C., Bonavida, B., & Park, N. (1997). Normal human oral keratinocytes are more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine-induced cytotoxicity and apoptosis than HPV-immortalized oral keratinocytes. International Journal of Oncology, 10, 47-51. https://doi.org/10.3892/ijo.10.1.47
MLA
Baek, J., Bertolami, C., Bonavida, B., Park, N."Normal human oral keratinocytes are more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine-induced cytotoxicity and apoptosis than HPV-immortalized oral keratinocytes". International Journal of Oncology 10.1 (1997): 47-51.
Chicago
Baek, J., Bertolami, C., Bonavida, B., Park, N."Normal human oral keratinocytes are more sensitive to N-methyl-N'-nitro-N-nitrosoguanidine-induced cytotoxicity and apoptosis than HPV-immortalized oral keratinocytes". International Journal of Oncology 10, no. 1 (1997): 47-51. https://doi.org/10.3892/ijo.10.1.47