Upregulation of telomerase activity by X-irradiation in mouse leukaemia cells is independent of Tert, Terc, Tnks and Myc transcription

X-irradiation of two mouse myeloid leukaemia cell lines was found to lead t o increased telomerase activities. Maximal increases in activity at 24 h po st-irradiation were approximately three times control unirradiated cell lev els. These maxima mere reached at between 3-5 Gy depending upon cell line, Peak activity was reached at 8 h, remained elevated to 24 h and returned to control levels by 48 h, In contrast, X-irradiation did not activate telome rase in a telomerase-negative human fibroblast line, while in cultured norm al mouse bone marrow cells irradiation appeared to reduce activities. No si mple relationship between radiation-induced increases in telomerase activit y in the myeloid leukaemia lines and the proportions of cells in the S or M phases of the cell cycle was apparent, Radiation-induced increases in acti vity were significantly reduced by inhibitors of transcription (actinomycin D, alpha-amanatin) and protein synthesis (cycloheximide). These data are c onsistent with two possibilities: (i) X-irradiation leads to increased tran scription and/or translation of a component of telomerase, thus increasing activities; or (ii) X-irradiation induces the transcription of a positive r egulator of telomerase activity: Northern blot analysis did not indicate th at transcription of mTert, the catalytic subunit of telomerase, or mTerc, t he RNA component, was elevated after irradiation. Similarly, no significant changes in the expression of Myc or Tnks, the tankyrase gene, two suspecte d telomerase regulators, were detected. These data are therefore consistent with the induction by X-irradiation of a positive regulator of telomerase activity other than Tab or Myc or the core protein and RNA components of th e enzyme.