RADIATION EFFECTS ON S-PHASE DURATION, LABELING INDEX, POTENTIAL DOUBLING TIME AND DNA DISTRIBUTION IN HEAD AND NECK-CANCER XENOGRAFTS

The effect of irradiation on S-phase duration (Ts), labelling index (L I), potential doubling time (Tpot), and cell cycle phase distributions was determined by DNA flow cytometry in xenografted human squamous ce ll carcinoma of the head and neck (SCCHN). Tumours were treated with a single dose of 3 Gy, and excised at intervals over a 90-h period. Six hours before each excision the tumours were labelled in vivo with bro modeoxyuridine (BrdUrd). Although the growth rate of irradiated tumour s was comparable with that of untreated controls, analysis of BrdUrd u ptake revealed a transient reduction of LI and a prolongation of Ts in irradiated tumours. Maximum mean Tpot was 931 days in irradiated tumo urs as compared to 13 days in untreated controls. The variations in Ts , LI and Tpot all occurred within the first hours after irradiation; d uring the remainder of the observation time, the values of the variabl es did not differ from those of untreated controls. In irradiated tumo urs the distribution of cells according to DNA content changed signifi cantly on three occasions during the observation period: 1) Parallel t o the initial lowering of LI and prolongation of Ts there was a transi ent increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S and G2; 2) At 18 h, the most pronounced cell cycle phase redistribution occurred when the G0/G1 fraction decreased and the S and G2 phase fractions increased; 3) At 66 h (i.e., approxi mately one cell cycle later), the pattern was the same as that after 1 8 h. The findings suggest that the transient prolongation of DNA repli cation seen in SCCHN cells immediately after a single radiation dose i s a symptom of DNA damage inflicted during late G1 or early S-phase, a nd that this disturbance in DNA synthesis is associated with the subse quent accumulation of cells in G2 phase.