RADIATIONRESEARCH 120, 213-226 (1989) Influence of Ionizing Radiation on Oxygen Profiles in Different Types of Multicellular Spheroids T. NYLEN,* H. ACKER,t B. BiLLING,t G. HOLTERMAN,t AND J. CARLSSONf *Division of Radiation Biology, Swedish Defence Research Establishment, FOA 4, S-901 82 Umed, Sweden; tMax-Planck Institutefor System Physiology, Rheinlanddamm 201, 4600 Dortmund, Federal Republic of Germany; and $Institute ofRadiation Sciences, Uppsala University, Box 535, S751 21 Uppsala, Sweden NYLEN, T., ACKER, H., BOLLING, B., HOLTERMAN, G., AND CARLSSON, J. Influence of Ioniz- ing Radiation on Oxygen Profiles in Different Types of Multicellular Spheroids. Radiat.Res. 120, 213-226(1989). Human glioma(U-118 MG and U-138 MG), humancolorectal adenocarcinoma (HT-29), human thyroid carcinoma (HTh 7), and hamster embryonic lung (V79-379A) spheroids were irradiated with either single doses of 16 or 40 Gy or fractionated doses of eight times 5 Gy. Oxygen profiles in the spheroids were measured withmicroelectrodes atdifferent times following irradiation, andthese profiles were then compared withthe oxygen profiles measured in parallel cultured nonirradiated spheroids. No significant radiation-induced changes in the oxygen pro- files were seen in any of the spheroids withinthe firstfew days afterirradiation. The glioma spheroids did not show any significant increase in oxygen tension even after longer times; how- ever,they were growth inhibited, and the number of S-phase cellswas strongly suppressed. In- creases in oxygen tensiondid occurin the HT-29 and V79-379A spheroids but only appeared more than a week after irradiation, when degeneration had started. Histological changes and decrease in diameter were seen in the spheroids that started to degenerate about 5 days after irradiation. Thus radiation doses in the therapeutic range did not, for the spheroids studied, produce rapid increases in the oxygen tension. Whena change occurred, it appeared rather late andwas probably a consequence of cell degeneration. ? 1989 Academic Press, Inc. INTRODUCTION The radioprotective effectof hypoxia in cells and tissuesis well-known (1, 2). The varying vascularization seen in different tumor types and between regions withinin- dividual tumors (3) introduces the riskthat the oxygen tension in some regions is so low that cells escape the effectsof radiation treatment (1). Since radiation imposes disturbances on tumor growth, it is questionable as to what extent reoxygenation occurs during the course of radiotherapy. From the resultsof studies of radiation sensitivity in transplanted tumors, there are strong indicationsthat reoxygenation actually takes place after irradiation. The mechanism is not exactly understood; how- ever, it may be the result of changes in blood flow, reduced oxygen utilization by radiation-damaged cells, or rapid cell loss (1). The aim of this work was to study radiation-induced changes in oxygen tension by measuring pO2 profiles in cultured spheroids with microelectrodes. Spheroids are three-dimensional cell aggregates of spherical shape thatresemble in vivo tumornod- 213 0033-7587/89 $3.00 Copyright ? 1989 by Academic Press, Inc. All rights of reproduction in any form reserved. Radiation Research Society is collaborating with JSTOR to digitize, preserve, and extend access to Radiation Research www.jstor.org ®