Matsushita S, Ando K, Koike S, Grdina D J, Furukawa S
Section of Laboratory Animals, National Institute of Radiological Sciences, Chiba, Japan.
Int J Radiat Oncol Biol Phys. 1994 Nov 15;30(4):867-72. doi: 10.1016/0360-3016(94)90362-x.
To evaluate the protective effect of WR-151327 on late radiation-induced damage to normal tissues in mice.
The right hind legs of mice with or without WR-151327 administration (400 mg/kg) were irradiated with 137Cs gamma rays. Leg contracture and skin shrinkage assays were performed at 380 days after irradiation. The mice were killed on day 400 postirradiation and histological sections of the legs were made. The thickness of the dermis, epidermis, and skin (dermis plus epidermis) was measured. The muscular area of the legs and the posterior knee angle between the femur and tibia were also measured. The left hind legs were similarly assessed as nonirradiated controls. Group means and standard deviations were calculated and dose-response curves were drawn for every endpoint. Then, the dose modifying factor (DMF) for each endpoint and the correlations among endpoints were determined.
Late damage assayed by leg contracture and skin shrinkage progressed with increasing radiation dose. However, it was reduced by drug treatment. The significant effect was indicated for skin shrinkage by a DMF of 1.8 at 35%. The DMF for leg contracture was 1.3 at 6 mm. In the irradiated legs, epidermal hyperplasia and dermal fibrosis in the skin, muscular atrophy, and extension disturbance of the knee joint were observed. These changes progressed with increasing radiation dose. Skin damage assayed by the present endpoints was also reduced by drug treatment by DMFs of 1.4 to 1.7. However, DMFs for damage to the muscle and knee were not determined because no isoeffect was observed. There were good correlations between leg contracture or skin shrinkage and the other endpoints in both untreated and drug-treated mice.
WR-151327 has the potential to protect against radiation-induced late normal tissue damage.
评估WR-151327对小鼠正常组织晚期辐射损伤的保护作用。
对给予或未给予WR-151327（400mg/kg）的小鼠右后肢进行137Csγ射线照射。在照射后380天进行腿部挛缩和皮肤收缩试验。在照射后第400天处死小鼠并制作腿部组织切片。测量真皮、表皮和皮肤（真皮加表皮）的厚度。还测量了腿部的肌肉面积以及股骨与胫骨之间的后膝角度。左后肢作为未照射对照进行同样评估。计算组均值和标准差，并为每个终点绘制剂量反应曲线。然后，确定每个终点的剂量修正因子（DMF）以及各终点之间的相关性。
通过腿部挛缩和皮肤收缩测定的晚期损伤随着辐射剂量增加而进展。然而，药物治疗使其减轻。对于皮肤收缩，在35%时DMF为1.8表明有显著效果。腿部挛缩在6mm时的DMF为1.3。在照射的腿部，观察到皮肤中的表皮增生和真皮纤维化、肌肉萎缩以及膝关节伸展障碍。这些变化随着辐射剂量增加而进展。通过本研究终点测定的皮肤损伤也因药物治疗而减轻，DMF为1.4至1.7。然而，由于未观察到等效应，未确定肌肉和膝关节损伤的DMF。在未治疗和药物治疗的小鼠中，腿部挛缩或皮肤收缩与其他终点之间均存在良好相关性。
WR-151327有潜力预防辐射诱导的正常组织晚期损伤。
