Chromosome end-to-end associations and telomerase activity during cancer progression in human cells after treatment with alpha-particles simulating radon progeny.
Chromosome end-to-end associations seen at metaphase involve telomeres and are commonly observed in cells derived from individuals with ataxia telangiectasia and most types of human tumors. The associations may arise because of short telomeres and/or alterations of chromatin structure. There is a growing consensus that telomere length is stabilized by the activity of telomerase in immortal cells; however, it is not clear why some immortal cells display chromosome end-to-end associations. In the present study we evaluated chromosome end-to-end associations, telomere length and telomerase activity with the tumorigenic status of human bronchial epithelial cells immortalized with human papillomavirus. Oncogenic transformation was initiated using radon simulated alpha-particles and cells evaluated as primary, secondary and metastatic transformants. The fewest chromosome end associations and lowest telomerase activity were observed in the parental immortalized cells. However, increased levels of telomerase activity were detected in alpha-particle survivors while robust telomerase activity was seen in the tumorigenic cell lines. The tumorigenic cells that were telomerase positive and had the highest frequency of cells with chromosome end-to-end associations were also metastatic. No correlation was found between telomere length and the different stages of carcinogenicity.
Pandita
T K
TK
Center for Radiological Research, Columbia University, New York, NY 10032, USA.
Hall
E J
EJ
Hei
T K
TK
Piatyszek
M A
MA
Wright
W E
WE
Piao
C Q
CQ
Pandita
R K
RK
Willey
J C
JC
Geard
C R
CR
Kastan
M B
MB
Shay
J W
JW
D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000473:pathology; D002461:Cell Line, Transformed / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics* / Q000473:pathology; D025063:Chromosome Disorders; D002875:Chromosomes / Q000528:radiation effects; D005347:Fibroblasts / Q000473:pathology; D016193:G1 Phase / Q000235:genetics; D016195:G2 Phase / Q000235:genetics; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D011886:Radon; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D019098:Telomerase; D011886:Radon