Filimonova M V, Ulyanenko S E, Shevchenko L I, Kuznetsova M N, Makarchuk V M, Chesnakova E A, Samsonova A S, Filimonov A S
Radiats Biol Radioecol. 2015 May-Jun;55(3):260-6.
We studied the effect of T1023, NO-synthase inhibitor, N-acyl-S-alkyl-isothiourea in a single administration at a dose of 75 mg/kg on the growth of transplantable rat sarcoma M-1 and the development of acute skin reactions after the local impact of γ-radiation at the doses of 32 and 36 Gy. The results showed that the T1023 at a single dose had no effect on the growth of sarcoma, and did not modify the radiosensitivity of the tumor and anti-tumor efficacy of γ-rays. However, at both doses T1023 significantly reduced the severity of acute radiation skin reactions. NOS inhibitor did not change the duration of the inflammatory and regenerative processes, but significantly limited the degree of radiation alteration of the deep layers of the skin and underlying tissues. The findings suggest that the hypoxic mechanism of antitumor action allows T1023 to selectively protect the non-malignant tissue during radiation therapy of solid tumors. Therefore, this compound may be regarded as a promising basis for the development of pharmacological prevention of radiotherapy complications.
我们研究了一氧化氮合酶抑制剂N-酰基-S-烷基异硫脲T1023以75mg/kg的剂量单次给药对可移植大鼠肉瘤M-1生长的影响,以及在32Gy和36Gy剂量的γ射线局部照射后急性皮肤反应的发生情况。结果表明,单次剂量的T1023对肉瘤生长没有影响,也未改变肿瘤的放射敏感性和γ射线的抗肿瘤疗效。然而,在这两个剂量下,T1023均显著降低了急性放射性皮肤反应的严重程度。一氧化氮合酶抑制剂并未改变炎症和再生过程的持续时间,但显著限制了皮肤深层和下层组织的放射改变程度。这些发现表明,抗肿瘤作用的缺氧机制使T1023在实体瘤放射治疗期间能够选择性地保护非恶性组织。因此,这种化合物可被视为开发放射治疗并发症药理学预防方法的有前景的基础。