Cell Kinetic Studies of the Effect of A Combined Therapy With 1-βd-Arabinofuranosylcytosine (Ara-C) and X-Irradiation On the L1210 Ascites Tumour

Abstract. We studied the effect of combined therapy with X-ray and 1-β-D-arabinofuranosylcytosine (Ara-C); firstly the effect of whole-body X-irradiation alone on the proliferation of the L1210 ascites tumour of the mouse was studied by autoradiographic and cytofluorometric (FCM) methods. the effect of X-irradiation with 4 Gy was mainly a cytostatic one leading to an altered distribution of the cells throughout the cycle due to radiation induced mitotic delay. the cytocidal effect is negligible.
As is known from previous studies (Fietkau, Friede & Maurer-Schultze, 1984) the effect of 200 mg/kg Ara-C consists of an inhibition of DNA synthesis and of killing a considerable portion of the L 1210 cells, predominantly of S phase cells.
With respect to the importance for potential therapeutic regimens, the influence of the sequence and the time interval between the two therapeutic steps on the survival of tumour-bearing mice was studied. Most combination therapies significantly increase the survival of tumour-bearing mice compared to the single therapeutic steps; however, no significant differences between the various combined therapies were found. Whole-body X-irradiation with 4 Gy followed by the application of 200 mg/kg Ara-C 10 hr later resulted in the greatest increase of the mean survival time of tumour-bearing animals, from 13.2 to 17.4 days. It was shown that apart from the cytocidal effect on S-phase cells, Ara-C also kills cells sublethally damaged by a preceding X-irradiation.