Nitric oxide produced by inducible nitric oxide synthase is associated with mammary tumorigenesis in irradiated rats
Nitric oxide produced by inducible nitric oxide synthase is associated with mammary tumorigenesis in irradiated rats
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DOI：
10.1016/j.niox.2004.10.010
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发表时间：
2005-02-01
影响因子：
3.9
通讯作者：
Onoda, M
中科院分区：
文献类型：
--
作者：
Inano, H;Onoda, M
本研究旨在探讨辐射诱导的一氧化氮合酶（NOS）产生的一氧化氮（NO）是否与乳腺肿瘤的发生有关。当大鼠在断奶后立即接受γ射线全身照射（1.5戈伊），然后用己烯雌酚治疗时，作为照射对照，肿瘤发生率（85%）与未照射对照（11.1%）相比增加了7.6倍。在照射前30 min腹腔注射诱导型一氧化氮合酶（iNOS）表达抑制剂和自旋捕获剂苯基-N-叔丁基硝酮（PBN，160 mg/kg），肿瘤发生率降至28.6%。此外，在照射后3天口服溶于饮用水的高选择性iNOS抑制剂N-（3-（氨甲基）-苄基）-乙酰胺（1400 W，2.3 +/- 0.1 mg/天）的大鼠中，肿瘤发生率（25%）低于照射对照组的三分之一。PBN或1400 W治疗时，未发生腺癌。许多乳腺肿瘤的发展，在辐射大鼠是阳性的雌激素受体（ER）。相反，ER未检测到从照射大鼠给予PBN或1400 W的肿瘤。这些结果表明，iNOS衍生的NO可能参与雌激素依赖性乳腺癌辐射后的形成。(C)2004年爱思唯尔公司All rights reserved.
This study evaluated whether nitric oxide (NO) derived from nitric oxide synthase (NOS) induced by radiation is associated with tumorigenesis in the mammary glands. When rats were exposed to whole-body irradiation with gamma-rays (1.5 Gy) immediately after weaning and then treated with diethylstilbestrol, as an irradiated control, the tumor incidence (85%) was increased 7.6-fold in comparison with that (11.1%) of the non-irradiated control. The tumor incidence declined to 28.6% in the rats injected intraperitoneally with phenyl-N-tert-butynitrone (PBN, 160 mg/kg), an inhibitor of inducible NOS (iNOS) expression and also a spin trapping agent, 30 min before irradiation. Also, the tumor incidence (25%) in rats orally administered with N-(3-(aminomethyl)-benzyl)-acetamide (1400W, 2.3 +/- 0.1 mg/day), a highly selective inhibitor of iNOS, dissolved in drinking water for 3 days after the irradiation was less than one-third of that in the irradiated control. On treatment with PBN or 1400W, no adenocarcinoma developed. Many of the mammary tumors that developed in the irradiated rats were positive for the estrogen receptor (ER). In contrast, ER was not detected in the tumors yielded from irradiated rats administered with PBN or 1400W. These results indicate that iNOS-derived NO may participate in the formation of estrogen-dependent mammary adenocarcinomas following radiation. (C) 2004 Elsevier Inc. All rights reserved.