Carcinogenesis, Vol. 21, No. 6, 1087-1095,
June 2000
© 2000 Oxford University Press
Cancer Biology |
Apoptosis and cytokine release induced by ionizing or ultraviolet B radiation in primary and immortalized human keratinocytes
1 MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton BN1 9RR,
2 ICRF Videomicroscopy Laboratory, PO Box 123, Lincoln's Inn Fields, London WC2A 3PX,
3 ICRF Molecular Oncology Laboratory, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS and
4 School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Moulsecoomb, Brighton BN2 4GJ, UK
We have compared the induction of apoptosis and cytokine release by UVB and 
-radiation in primary (untransformed) and in two immortalized human epithelial/keratinocyte cell lines, HaCaT and KB (KB is now known to be a subline of the ubiquitous keratin-forming tumour cell line HeLa and we therefore designate it HeLa-KB). In both the primary and the immortalized cell lines apoptosis and release of the inflammatory cytokine interleukin-6 are induced rapidly following UVB irradiation. In contrast, only the immortalized cells undergo apoptosis and release interleukin-6 after -irradiation and here the onset of apoptosis and cytokine release are delayed. The same distinction between primary and immortalized cells was observed when double-strand breaks were induced with the anticancer drug mitoxantrone, which stabilizes topoisomerase II-cleavable complexes. We suggest that immortalization may sensitize keratinocytes to the apoptogenic effect of ionizing radiation or mitoxantrone by deregulating normal cell cycle checkpoints. In both human keratinocytes and fibroblasts, cell killing, as assayed by loss of colony-forming ability, is not coupled to apoptosis. Immortalization increases resistance to -radiation killing but sensitizes to apoptosis. In contrast, although immortalization also sensitizes to UVB-induced apoptosis, it does not affect UVB-induced cell killing. Apoptosis unambiguously indicates death at the single cell level but clonal cell survival integrates all the cellular and genetic processes which prevent or permit a scorable clone to develop.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. H. Wu, J. B. Wilson, A. M. Wolfreys, A. Scott, and N. J. Jones Optimization of the comet assay for the sensitive detection of PUVA-induced DNA interstrand cross-links Mutagenesis, March 1, 2009; 24(2): 173 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Hovest, N. Bruggenolte, K. S. Hosseini, T. Krieg, and G. Herrmann Senescence of Human Fibroblasts after Psoralen Photoactivation Is Mediated by ATR Kinase and Persistent DNA Damage Foci at Telomeres Mol. Biol. Cell, April 1, 2006; 17(4): 1758 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. He, J.-L. Huang, D. C. Ramirez, and C. F. Chignell Role of Reduced Glutathione Efflux in Apoptosis of Immortalized Human Keratinocytes Induced by UVA J. Biol. Chem., February 28, 2003; 278(10): 8058 - 8064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. DiRenzo, S. Signoretti, N. Nakamura, R. Rivera-Gonzalez, W. Sellers, M. Loda, and M. Brown Growth Factor Requirements and Basal Phenotype of an Immortalized Mammary Epithelial Cell Line Cancer Res., January 1, 2002; 62(1): 89 - 98. [Abstract] [Full Text] [PDF]
|
|