The sole purpose of radio-contrast agents is to increase the absorption of X rays in blood vessels and soft tissues. Current diagnostic agents take advantage of the properties of iodine with its acceptably low clinical toxicity and moderately high atomic number (53), the latter yielding a relatively large absorption coefficient for photons in the diagnostic X-ray energy range, owing to the photoelectric effect. One consequence of this, not often appreciated, is that cells in the vicinity of an iodine-rich solution will receive a higher radiation dose than would be the case if iodine were not present. This is partly responsible for the reported cytogenetic changes in lymphocytes in vitro and in vivo (Adams et al, 1977;Norman et al, 1978;Cochran et al, 1980;Cochran & Norman, 1982;Hadaghy et al, 1982). Though these data clearly signal an undesirable, if unavoidable, phenomenon in diagnostic radiology, such a cytotoxic effect may be capable of exploitation in radiotherapy.To examine this latter possibility, cells in vitro were treated with various concentrations of the contrast agent meglumine ioglycamide (Biligram, Schering AG) and subjected to orthovoltage X rays. Marked radiation enhancement was obtained at an iodine concentration of 50mg ml" 1 , a concentration that is well within the range achievable in the bloodstream.
METHODChinese hamster ovary (CHO) cells were grown in monolayer culture in Hepes-buffered minimum essential medium (MEM) supplemented with 15% fetal calf serum, nonessential amino acids and L-glutamine. Tissue culture flasks (25 cm 2 ; Nunclon) were seeded with 3.5 x 10 5 cells 24 h before irradiation, so that cells were in the exponential phase of growth during treatment.Biligram was obtained as a 17% aqueous solution (85 mg ml" 1 iodine) and diluted with complete medium to the required concentration. Biligram cannot pass through the cell membrane and a 10% aqueous solution was not cytotoxic towards a cell monolayer for 1 h at 37°C. Monolayers of CHO cells were given 5 or 10 ml of fresh complete medium (depth of medium 2 or 4 mm above cell monolayer), containing the necessary quantity of Biligram, 5 min before irradiation.Cell monolayers growing on the bottom of flat plastic flasks were irradiated from above with X rays generated at 250 kVp (half value layer 0.83 mm Cu) and at a dose-rate of 1.60 cGy min ~1. The incident beam passed through 4 mm of iodine-rich medium before reaching the cell layer.In a further experiment, to examine the importance of the direction of the incident beam in relation to the iodine-rich medium and cell layer, the monolayer was irradiated from below, i.e. the X-ray beam passed through the bottom of the dish and the cells before traversing the overlying layer of medium (2 mm deep). The dose-rate for this irradiation was 1.81 cGy min" 1 .The experiment was repeated with photons from a cobalt-60 source (1.25 MeV) to confirm that there is little enhancement at this energy where photoelectric absorption is minimal. In this case, cells were irradiated from above at a dose-r...