Abstract

By means of growth delay measurements, the in vivo radiation response of three recently established human cervix carcinoma xenograft lines has been determined at both high (70 cGy/min) and low dose rate (5 cGy/min). In addition, we have investigated the role of the polyADP-ribosylation inhibitor, 3-aminobenzamide, (3-AB, administered at 450 mg/kg) in modifying the xenograft response to continuous low dose rate irradiation (5 cGy/min). For all three lines, less growth delay was observed for 9 Gy administered at 5 cGy/min compared to 70 cGy/min; in terms of the times for tumours to reach twice their original weight ( T 2 values), low dose rate effect sparing ratios of 2.1 for HX 155, 1.5 for HX 156 and 2.4 for HX 160 were observed. 3-AB exerted no significant effect on the growth of unirradiated tumours. When 3-AB was given during irradiation at 5 cGy/min to 9 Gy, an enhancement in growth delay was observed for each line. However, the degree of radioenhancement by 3-AB varied among the lines; significant enhancement ( p < 0.01) at all time points tested was observed for HX 156, while for the other two lines, the degree of enhancement was not significant. Enhancement effect ratios (in terms of T 2 values) were 1.37 for HX 155, 1.55 for HX 156 and 1.02 for HX 160. Similar differential radiosensitising effects with 3-AB have been observed previously in vitro. More potent poly(ADP-ribosylation) inhibitors are probably required along with additional normal tissue studies before such an approach may be proposed at the clinical level.

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