Meistrich M L, Finch M V, Hunter N, Milas L
Int J Radiat Oncol Biol Phys. 1984 Sep;10(9):1551-4. doi: 10.1016/0360-3016(84)90501-7.
WR-2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid) has been demonstrated to be cytotoxic to stem spermatogonia in the mouse. Five and 10 injections of 300 mg/kg killed sufficient numbers of stem cells to reduce sperm production 56 days after treatment by 16 and 43%, respectively. Single injections of 300 or 400 mg/kg of WR-2721 given 15 min after irradiation produced negligible toxicity to stem cells as measured by counts of repopulated tubules; 600 mg/kg reduced stem cell survival by 47%. Four daily injections of 300 mg/kg given 4, 3, 2, and 1 days prior to irradiation (with or without a fifth injection 15 min after irradiation) reduced stem cell survival by about 60%. The cytotoxic effects of WR-2721 on testicular stem cells at least partially explains the reduced protection factors observed in the testis with low doses of radiation and during fractionated treatments involving multiple injections of drug.
WR-2721(S-2-(3-氨丙基氨基)乙硫代磷酸)已被证明对小鼠精原干细胞具有细胞毒性。以300mg/kg的剂量注射5次和10次,足以杀死大量的干细胞,使治疗后56天的精子产量分别降低16%和43%。照射后15分钟单次注射300或400mg/kg的WR-2721,通过再填充小管计数测量,对干细胞产生的毒性可忽略不计;600mg/kg使干细胞存活率降低47%。在照射前4天、3天、2天和1天每天注射300mg/kg(照射后15分钟有无第五次注射均可),可使干细胞存活率降低约60%。WR-2721对睾丸干细胞的细胞毒性至少部分解释了在低剂量辐射和多次注射药物的分次治疗过程中,在睾丸中观察到的保护因子降低的现象。