Radiotherapeutic response of Ehrlich ascites tumor cells perfused in agarose gel threads and implanted in mice. A 31P MR spectroscopy study.
OBJECTIVE
In order to obtain better understanding of radiation-induced alterations in intracellular metabolism, a dynamic and non-invasive experimental model system is required. A serial study in cultured tumor cell line followed by verification in the in vivo samples may be of considerable value for non-invasive prediction and/or detection of tumor response to therapy. The present study was undertaken to evaluate the radiation response of perfused Ehrlich ascites tumors cells (EATC) immobilized in agarose gel matrix to that observed in mouse bearing EATC tumor, in order to identify biomarkers of radiation response.


METHODS
Perfused EAT cells, entrapped in agarose gel threads were irradiated in the perfusion assembly outside the magnet with fast electrons (6 Gy, 1 Gy/min) using 30 MeV Betatron. Solid EATC tumors implanted subcutaneously onto right hand limb of Swiss-albino strain "A" mice, were focally irradiated using 60Co teletherapy (10 Gy, 0.4 Gy/min). Metabolites changes were monitored by 31P MR spectroscopic techniques.


RESULTS
A post-irradiation decrease in the levels of ATP and ADP along with an increase in inorganic phosphate and glycerophosphocholine levels was observed. The ratios of beta-phosphate of ATP to inorganic phosphate (beta-ATP/Pi), and phosphocholine to glycerophosphocholine (PC/GPC), declined during 1-5 hours following irradiation, in perfused EAT cells and in the solid tumors implanted in mice.


CONCLUSIONS
Perfused cells could be used as a simple model of tumor for prediction of clinical radiotherapeutic response. The present study demonstrates that radiation damage may be occurring both at the DNA protein as well as the membrane lipid levels. Therefore, the bioenergetics and phospholipid profiles of tumor cells could be used as complimentary, reliable and sensitive indirect indicators for devising predictive assays for assessment and monitoring of radiation response, which will also facilitate the individualization and optimization of tumor radiotherapy.
Sharma
R K
RK
Institute of Nuclear Medicine and Allied Sciences, Delhi. rks@drinma.ren.nic.in
Jain
V
V
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000532:radiotherapy*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D010759:Phosphorus Isotopes; D010767:Phosphorylcholine / Q000378:metabolism; D011237:Predictive Value of Tests; D012685:Sepharose; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D010759:Phosphorus Isotopes; D010767:Phosphorylcholine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D012685:Sepharose