Travis E L, Parkins C S, Holmes S J, Down J D, Fowler J F
Int J Radiat Oncol Biol Phys. 1984 Feb;10(2):243-51. doi: 10.1016/0360-3016(84)90010-5.
The radioprotective effect of WR-2721 has been studied in mouse lung after single doses of radiation. Using the breathing rate assay and lethality, radioprotection was assessed at monthly intervals between 3 and 18 months after irradiation during both pneumonitis and chronic fibrosis. The degree of radioprotection was greater for fibrosis than for pneumonitis using both assays. In replicate experiments, dose modifying factors (DMF's) ranging from 1.2 to 1.4 were obtained for pneumonitis and 1.5 and 1.6 for fibrosis. The differences in DMF's for the two phases of lung damage were significant. A difference in the time course of expression of damage was seen in both the breathing rate and lethality assays between mice irradiated with and without WR-2721: the damage ended sooner in the drug-treated mice. This difference is best explained by protection of all damage after 5 months by WR-2721. No evidence of drug toxicity was found. We conclude that WR-2721 protects against chronic lung fibrosis caused by radiation at least as well as against the earlier appearing pneumonitis after single doses of radiation. Thus, if WR-2721 is dose modifying and if late tissue complications are dose limiting in clinical radiotherapy, then a therapeutic benefit would be obtained by the use of this drug in clinical radiotherapy, provided that the radioprotection of tumors did not exceed a factor of 1.5-1.6.
WR-2721对单次辐射后小鼠肺部的辐射防护作用已得到研究。采用呼吸频率测定法和致死率测定法，在辐射后3至18个月期间，每隔一个月对肺炎期和慢性纤维化期的辐射防护作用进行评估。使用这两种测定法时，纤维化期的辐射防护程度均高于肺炎期。在重复实验中，肺炎期的剂量修正因子（DMF）范围为1.2至1.4，纤维化期为1.5至1.6。肺部损伤两个阶段的DMF差异具有显著性。在呼吸频率测定法和致死率测定法中，接受WR-2721照射和未接受照射的小鼠在损伤表达的时间进程上均存在差异：药物处理组小鼠的损伤结束得更快。这种差异最好的解释是WR-2721在5个月后对所有损伤均有防护作用。未发现药物毒性的证据。我们得出结论，WR-2721对单次辐射引起的慢性肺纤维化的防护作用至少与对早期出现的肺炎的防护作用相同。因此，如果WR-2721具有剂量修正作用，并且如果晚期组织并发症在临床放射治疗中是剂量限制因素，那么在临床放射治疗中使用这种药物将获得治疗益处，前提是对肿瘤的辐射防护不超过1.5 - 1.6倍。
