[Radioprotective Properties of NO-synthase Inhibitor T1023: II. The Ability for Selective Protection of Normal Tissues During Radiotherapy of Tumors].

M V Filimonova, S E Ulyanenko, L I Shevchenko, M N Kuznetsova, V M Makarchuk, E A Chesnakova, A S Samsonova, A S Filimonov
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Abstract

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.

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no -合成酶抑制剂T1023的辐射防护性能[j]。肿瘤放疗中正常组织的选择性保护能力[j]。
研究了no合酶抑制剂T1023、n -酰基-s -烷基-异硫脲单次给药75 mg/kg剂量对可移植大鼠M-1肉瘤生长的影响以及32和36 Gy γ辐射局部照射后急性皮肤反应的发生。结果表明,单剂量T1023对肉瘤的生长没有影响,也没有改变肿瘤的放射敏感性和γ射线的抗肿瘤疗效。然而,在两种剂量下,T1023都显著降低了急性辐射皮肤反应的严重程度。NOS抑制剂没有改变炎症和再生过程的持续时间,但明显限制了皮肤深层和下层组织的辐射改变程度。研究结果提示,T1023抗肿瘤作用的缺氧机制使其在实体瘤放射治疗中选择性保护非恶性组织。因此,该化合物可能被视为放射治疗并发症药理预防发展的有希望的基础。
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