TY - JOUR
T1 - Evaluation of the gene for inducible nitric oxide synthase as a radiosensitizer under hypoxic and oxic conditions
AU - Turek, M.
AU - Padilla, M.
AU - Argyle, D.J.
N1 - Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/1/1
Y1 - 2007/1/1
N2 - The radiosensitizing effect of inducible nitric oxide synthase (iNOS) was evaluated, in vitro , in a feline vaccine-associated sarcoma (VAS) cell line and a canine osteosarcoma cell line (D17). The gene encoding the human iNOS was cloned into an expression plasmid under the control of a cytomegalovirus immediate early promoter. Transient transfections were performed in feline VAS cells and D17 cells. Nitric oxide was measured in the supernatant media 48h later as an indirect measurement of iNOS expression. Cells were irradiated using cobalt-60 under hypoxic or oxic conditions, and clonogenic assays were used to evaluate the effects of gene transfer on the sensitivity of cells to radiation. The results demonstrated that iNOS had no significant effect on improving the radiosensitivity of cells under oxic conditions. However, under hypoxic conditions, iNOS gene transfer significantly improved radiosensitization in osteosarcoma cells. These results demonstrate the feasibility of improving the outcome of radiotherapy in dogs with large bulky tumours using iNOS gene therapy.
AB - The radiosensitizing effect of inducible nitric oxide synthase (iNOS) was evaluated, in vitro , in a feline vaccine-associated sarcoma (VAS) cell line and a canine osteosarcoma cell line (D17). The gene encoding the human iNOS was cloned into an expression plasmid under the control of a cytomegalovirus immediate early promoter. Transient transfections were performed in feline VAS cells and D17 cells. Nitric oxide was measured in the supernatant media 48h later as an indirect measurement of iNOS expression. Cells were irradiated using cobalt-60 under hypoxic or oxic conditions, and clonogenic assays were used to evaluate the effects of gene transfer on the sensitivity of cells to radiation. The results demonstrated that iNOS had no significant effect on improving the radiosensitivity of cells under oxic conditions. However, under hypoxic conditions, iNOS gene transfer significantly improved radiosensitization in osteosarcoma cells. These results demonstrate the feasibility of improving the outcome of radiotherapy in dogs with large bulky tumours using iNOS gene therapy.
UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-68949118151&md5=2c8dae28b9fe3dfcc897ae67c0b5804e
U2 - 10.1111/j.1476-5829.2007.00138.x
DO - 10.1111/j.1476-5829.2007.00138.x
M3 - Article
AN - SCOPUS:68949118151
SN - 1476-5810
VL - 5
SP - 250
EP - 255
JO - Veterinary and Comparative Oncology
JF - Veterinary and Comparative Oncology
IS - 4
ER -