Induction of telomerase activity by UV-irradiation in Chinese hamster cells

Abstract

Telomerase is a ribonucleoprotein whose activity has been detected in germline cells and in neoplastic and immortal cells. Telomerase compensates the telomere loss arising by the end replication problem by synthesizing telomeric repeats at the 3' end of the eukaryotic chromosomes. Telomerase is reactivated during cancer progression in human and mice. In order to determine whether the telomerase activity can be upregulated in vitro in response to DNA damaging agents, we examined the telomerase activity in ®ve Chinese hamster cell lines following exposure to 5 J/m 2 or 40 J/m 2 UV-C radiation. All the cell lines tested showed an increase in telomerase activity in the PCRbased telomeric repeat ampli®cation protocol (TRAP) in a dose dependent manner. This increase in telomerase activity correlated well with the number of cells being in the S and G 2 /M phase after UV exposure. However, in unirradiated control cells, similar levels of telomerase activity were observed in di erent phases of the cell cycle. Furthermore, telomeric signals were clustered in one or more parts of the disintegrating nuclear particles of the apoptotic cell as detected by¯uorescence in situ hybridization (FISH). This is the ®rst study to demonstrate the induction of telomerase activity following exposure to DNA-damaging agents like UV radiation in Chinese hamster cells in vitro.

Rapid upregulation of telomerase activity in human leukemia HL-60 cells treated with clinical doses of the DNA-damaging drug etoposide

“…Early upregulation has previously been reported in irradiated mouse and human hematopoietic cell lines. 26,31 In agreement with our results, several radiation studies also noted large increases in telomerase activity 24 h after treatment, as well as dose-dependent hyperactivation [26][27][28]31,32 that plateaus at higher doses. 26,28 The magnitude of telomerase upregulation observed in our study is similar to the increases in activity reported for X-irradiated human colorectal carcinoma cell lines.…”

“…One hypothesis is that telomerase upregulation may constitute part of the cellular response to DNA damage, as telomerase upregulation has been reported only in cells exposed to DNA-damaging treatments such as radiation. [26][27][28][31][32][33] This hypothesis is supported by our data, which showed that telomerase upregulation occurred only in cells that undergo an extensive period of cell cycle arrest prior to cell death, a type of response that is characteristic of the DNA damage repair process. 42 Double-stranded DNA breakinducing treatments result in broken chromosomes that may mimic exposed or dysfunctional telomeres.…”

“…[26][27][28][29][30][31][32][33][34] Telomerase-negative mice with short telomeres are more sensitive to ionizing radiation than their telomerase-positive counterparts, and their cells sustain increased chromosomal damage and apoptosis. 11 Thus, telomerase activity and telomere integrity may confer protection against radiation in vivo, and might enhance the resistance of human tumor cells to anti-cancer treatments.…”

Phosphoinositide 3-Kinase/AKT1 Pathway and Human Ovarian Cancer

“…Induced telomerase activity progressively decreased in FHIOSE cells by 48 h after UV or DMSO treatment, while induced telomerase activity in SW626 cells returned to controls levels by 24 h after treatment. These results are in agreement with previous observations reporting a strong association between telomerase activity with sun exposure [53], a UV dose-dependent induction of telomerase activity in CHO cells [54], and restoration of basal telomerase levels within 24 h following withdrawal of DMSO [61]. We used our model system to identify some of the components that may regulate telomerase activity.…”

Phosphoinositide 3-Kinase/AKT1 Pathway and Human Ovarian Cancer

“…UV and DMSO were deemed to be potential modulators of telomerase activity in ovarian epithelial cell lines based upon our current understanding of telomerase regulation and ovarian neoplastic progression. Specifically, since Ueda et al reported increased telomerase activity following UV exposure of normal skin [53] and Hände et al reported a dose-dependent increase in telomerase activity following UV treatment in CHO cells [54], we sought to determine whether UV could induce telomerase activity in ovarian epithelial cell lines. Further, in contrast to carcinomas of most other tissues that de-differentiate with neoplastic progression, ovarian cancer progression is associated with the acquisition of morphological features characteristic of the endocervix, endometrium, and oviduct owing to their common embryonic origin [55][56][57].…”