The effect of 3-aminobenzamide in the radiation response of three human cervix carcinoma xenografts.
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 (T2 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 less than 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 T2 values) were 1.37 for HX 155, 1.55 for HX 156 and 1.02 for HX 160. Similar differential radiosensitizing 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.
Kelland
L R
LR
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, U.K.
Tonkin
K S
KS
D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D002277:Carcinoma / Q000532:radiotherapy*; D003037:Cobalt Radioisotopes / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy*
D001549:Benzamides; D003037:Cobalt Radioisotopes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents; C025160:3-aminobenzamide