Clonal cell populations unresponsive to radiosensitization induced by telomerase inhibition.
A combination of a radiotherapeutic regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC-/- cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC-/- clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening.
Ju
Yeun-Jin
YJ
Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
Shin
Hyun-Jin
HJ
Park
Jeong-Eun
JE
Juhn
Kyoung-Mi
KM
Woo
Seon Rang
SR
Kim
Hee-Young
HY
Han
Young-Hoon
YH
Hwang
Sang-Gu
SG
Hong
Sung-Hee
SH
Kang
Chang-Mo
CM
Yoo
Young-Do
YD
Park
Won-Bong
WB
Cho
Myung-Haing
MH
Park
Gil Hong
GH
Lee
Kee-Ho
KH
D000818:Animals; D002999:Clone Cells; D005347:Fibroblasts / Q000201:enzymology / Q000528:radiation effects; D051379:Mice; D008817:Mice, Mutant Strains; D011836:Radiation Tolerance; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D016615:Telomere / Q000378:metabolism*
D019098:Telomerase