UPTAKE, TOXICITY AND RADIATION EFFECTS OF THE BORON-COMPOUNDS DAAC-1 AND DAC-1 IN CULTURED HUMAN GLIOMA-CELLS

Purpose: To study the uptake, toxicity and radiation effects in vitro of a diol-amino acid-carborane (DAAC-I) and make comparisons with the previously studied diol-amine-carborane (DAC-I). Materials and methods : Toxicity and radiation effects were studied with clonogenic survival , uptake by measuring the cellular boron content and the subcellular d istribution was investigated after organelle separation with centrifug ation. The studied cell line was human glioma U343. Results: DAAC-I sh owed an accumulation of 1-1.5 times, compared with the culture medium, and was non-toxic up to 47 mu g boron/ml. The accumulation of DAC-I w as about 90 times, but toxic effects were detectable already at the co ncentration 5 mu g boron/ml. None of the compounds was localized in th e cell nucleus. Following irradiation with thermal neutrons, DEC-I was about 2.5 times more effective than DAAC-1 and about 4.9 times more e ffective than neutrons alone, at the survival level 0.2. The dose modi fying factors, when compared with the neutron beam alone, were for bot h DAAC-1 and DAC-1 about 1.5 and about 5 when compared with Co-60-gamm a-radiation. Conclusions: DAAC-1 was less toxic than DAC-1 but gave le ss accumulation of boron. Both substances gave significant boron-depen dent cell inactivation when the lest cells were exposed to thermal neu trons.