[Inhibitory effect of telomerase inhibitors combined with X-irradiation on bone marrow hematopoiesis in mice].
The purpose of this study was to evaluate the effect of telomerase inhibitors combined with X-irradiation on bone marrow hematopoiesis in tumor-carrying mice. With an orthogonal experiment design, the telomerase inhibitors [azidothymidine, AZT 300 mg/(kg.day) and lamivudine 150 mg/(kg x day), per os, bid, x 2 weeks] and X-irradiation [total dose 10 Gy (2 Gy x 5) in 1 week] were used to treat BALB/c mice carrying breast cancer MA(782) for evaluating the influence on peripheral blood cells, bone marrow nucleated cells and telomerase activity. Telomerase activity was detected by a PCR-based telomeric repeat amplification protocol (TRAP) coupled with ELISA. The results showed that the number of marrow nucleated cells (x 10(7)/femur) was 2.1875 in untreated group, and 1.7375, 1.7500 and 1.3475 in irradiated, lamivudine and AZT groups, respectively, these suggested that AZT and irradiation could obviously decrease the number of marrow nucleated cells (P< 0.01 or P < 0.05). The peripheral WBC increased 3.7% in untreated mice, and irradiation, lamivudine and AZT reduced 18.09%, 16.19% and 41.00% of WBC, respectively (P < 0.05). Irradiation, lamivudine and AZT showed no obvious effect on RBC and platelet counts (P > 0.05). The telomerase activity (A(450) nm) of marrow cells was 1.498, 1.483, 0.816 and 0.727 in untreated, irradiation, lamivudine and AZT groups, respectively. It is concluded that AZT and lamivudine combined with X-irradiation inhibit bone marrow nucleate cells and the peripheral WBC, manifest inhibitory effect on telomerase activity in murine bone marrow, but have no effect on the peripheral RBC and platelet.
Ruan
Xiao-Feng
XF
The Oncology Department of Xiangfan Central Hospital, Xiangfan 441021, China.
Xue
Ming-Hui
MH
Zhou
Yun-Feng
YF
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects*; D019259:Lamivudine / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014965:X-Rays; D015215:Zidovudine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019098:Telomerase