Stewart F A, Lundbeck F, Oussoren Y, Luts A
Experimental Therapy (H6), The Netherlands Cancer Institute, Amsterdam.
Int J Radiat Oncol Biol Phys. 1991 Oct;21(5):1211-9. doi: 10.1016/0360-3016(91)90278-c.
Functional damage in the mouse bladder was measured sequentially from 1 to 53 weeks after irradiation with a range of X ray doses (10 to 30 Gy). Damage was assessed from the independent assays of urination frequency and cystometric measurement of bladder volume at a constant intravesical pressure. There was an early, transient wave of damage from 1 to 3 weeks after bladder irradiation. During this period the urination frequency was increased to greater than or equal to 2 times control levels in 20 to 70% of the mice (depending on dose) after 15 to 30 Gy. Bladder volume was reduced to less than or equal to 50% of control values in 20 to 40% of the mice after doses of 20 to 30 Gy. This early damage usually lasted for less than 1 week and occurred at times ranging from 5 to 21 days, independent of dose. There was no significant correlation between response as measured by the two assays on an individual animal basis during the early period. The incidence of reduced bladder volume, measured cystometrically in anesthetized mice, tended to be less than the incidence of increased urination frequency, measured in non-anesthetized animals. Late bladder damage developed from 16 to 40 weeks after doses of greater than or equal to 20 Gy, and the time of onset was inversely related to dose. Less than 20% of mice treated with 10 to 15 Gy developed late bladder damage as assessed by increased urination frequency or reduced bladder volume. Late bladder damage was irreversible and there was a good correlation between response of individual animals as measured by the two assays. We conclude that changes in both urination frequency and bladder volume can be used as quantitative measures of early and late functional damage after bladder irradiation. The early, transient damage was not associated with changes in the urothelium or muscle layers of the bladder, whereas the late, persistent damage was accompanied by epithelial denudation and focal hyperplasia, with fibrosis and ulceration after higher doses.
在用一系列X射线剂量（10至30 Gy）照射后，从1至53周对小鼠膀胱的功能损伤进行了连续测量。通过排尿频率的独立测定以及在恒定膀胱内压下膀胱容量的膀胱测压测量来评估损伤情况。膀胱照射后1至3周出现早期短暂性损伤波。在此期间，15至30 Gy照射后，20%至70%的小鼠（取决于剂量）排尿频率增加至对照水平的2倍或更高。20至30 Gy剂量后，20%至40%的小鼠膀胱容量减少至对照值的50%或更低。这种早期损伤通常持续不到1周，发生时间为5至21天，与剂量无关。在早期，基于个体动物通过两种测定方法测量的反应之间没有显著相关性。在麻醉小鼠中通过膀胱测压测量的膀胱容量减少的发生率往往低于在未麻醉动物中测量的排尿频率增加的发生率。大于或等于20 Gy剂量后16至40周出现晚期膀胱损伤，且发病时间与剂量呈负相关。用10至15 Gy治疗的小鼠中，通过排尿频率增加或膀胱容量减少评估，不到20%的小鼠出现晚期膀胱损伤。晚期膀胱损伤是不可逆的，通过两种测定方法测量的个体动物反应之间存在良好的相关性。我们得出结论，排尿频率和膀胱容量的变化都可以用作膀胱照射后早期和晚期功能损伤的定量指标。早期短暂性损伤与膀胱的尿路上皮或肌肉层变化无关，而晚期持续性损伤伴有上皮剥脱和局灶性增生，高剂量后伴有纤维化和溃疡形成。
