Abstract
Early and late changes in the reservoir function of the mouse bladder were investigated after radiation alone or a combination of radiation and cisplatinum (cis-DDP). Bladder function was investigated by repeated cystometries. Treatments consisted of either single fraction radiation (5-10-15-25-30 Gy) or 20 Gy in combination with cis-DDP (6 mg kg-1; i.p.) administered at various time intervals from 14 days before until 14 days after radiation. At two selected time intervals (15 min and 4 h before) radiation was given at different dose levels (5-10-15-20 Gy). Within 30 days after irradiation a dose-dependent early response was noticed both in the radiation alone group and the group where cis-DDP was administered 15 min before radiation. The dose-response curve showed a slight but non-significant shift to the left in the combined treatment group (dose effect factor (DEF) = 1.18). Investigation of the early change in bladder reservoir function in the animals treated with 20 Gy alone or a combination of 20 Gy plus cis-DDP at various intervals in relation to irradiation demonstrated a significant increase in response when cis-DDP was administered 24 h and 15 min before and 4 h, 72 h and 336 h after 20 Gy (P less than 0.05). The reversible nature of the early damage was demonstrated. Late response was irreversible and significantly increased in most groups were cis-DDP was administered from 168 h before until 72 h after compared to radiation alone. Comparing groups treated with radiation alone with groups where cis-DDP was administered 15 min and 4 h before radiation revealed DEF values up to 1.45 (P less than 0.05), reflecting the significantly larger response in combined treatment groups. Survival was significantly decreased in all combined treatment groups compared to groups treated with radiation only and likewise survival was decreased in the group treated by cis-DDP alone compared to control (no treatment at all).
Highlights
A 50% decrease in the median urinary bladder pretreatment volume was used as the endpoint to illustrate the early and long term normal tissue changes after radiation alone compared to the radiation response when combined with cis-DDP at various time intervals
Our study on the effect of varying the interval between cis-DDP and irradiation indicates an increased response in the combined treatment groups compared to radiation alone in a rather wide time interval, i.e., administering cis-DDP from 24 h before until 336 h after radiation (Figure 1), with some few exceptions
This time interval is somewhat different from other reports (Von der Maase, 1986; Pearson & Steel, 1984) where an increased response was produced only at tighter intervals between cis-DDP and irradiation
Summary
All experiments were performed using female C3D2F,/Bom mice (C3H/Tif? x DBA/2d). The mice were 12-14 weeks old at the start of the experiments and weighed 20-25 g. All experiments were performed using female C3D2F,/Bom mice The mice were 12-14 weeks old at the start of the experiments and weighed 20-25 g. They were housed six per cage and given a standard laboratory diet and tap water ad libitum. Mice were anaesthetised (pentobarbital, 60 mg kg-'), and the bladder emptied of urine by use of a transurethral catheter. The mouse was restrained in a plexiglass cylinder snugly fitting into a lead box designed so as to shield the mouse completely except for an oval portal (13 by 8 mm) on each side, allowing irradiation of the urinary bladder on two opposing lateral fields. X-rays were generated with a 250 kV constant potential
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