Role of nitric oxide in radiation-induced initiation of mammary tumorigenesis in rats
Role of nitric oxide in radiation-induced initiation of mammary tumorigenesis in rats
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DOI：
10.1016/s1089-8603(03)00014-4
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发表时间：
2003-03-01
影响因子：
3.9
通讯作者：
Onoda, M
中科院分区：
文献类型：
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作者：
Inano, H;Onoda, M
一氧化氮（NO）及其反应产物已被证明会导致DNA损伤和致突变。为了阐明照射产生的NO是否参与乳腺肿瘤的发生，我们使用一氧化氮特异性清除剂Fe 2 +-二乙基二硫代氨基甲酸盐复合物（Fe（DETC）（2））或诱导型一氧化氮合酶（iNOS）的选择性抑制剂S，S '-（4-亚苯基-双（1，2-乙二啶基））双异硫氰酸酯（1，4-PB-ITU）进行了实验。哺乳期第21天的母鼠同时腹腔注射二乙基二硫代氨基甲酸盐和皮下注射Fe 2 +-柠檬酸盐以在体内形成Fe（DETC）（2），然后在注射后立即用1.5戈伊γ射线照射。以相同的方式在照射后8小时和24小时再注射化学品两次。然后将己烯雌酚颗粒作为肿瘤促进剂植入对照组和治疗组大鼠。实验组的乳腺肿瘤发病率明显降低，仅为对照组的1/4。另一方面，当母鼠在哺乳期第21天从照射前3天开始饮用含有0.005%1，4-PB-ITU的饮用水6天时，在1年期间观察到iNOS通道治疗组中的低肿瘤发病率。本研究首次证实，诱导型一氧化氮合酶（iNOS）产生的一氧化氮（NO）是辐射诱发大鼠乳腺肿瘤发生的重要自由基。(C)2002 Elsevier Science（美国）。All rights reserved.
Nitric oxide (NO) and its reaction products have been shown to cause DNA damage and to be mutagenic. To elucidate whether NO produced by irradiation participates in the initiation of mammary tumorigenesis, we performed experiments using the nitric oxide-specific scavenger Fe2+-diethyidithiocarbamate complex (Fe(DETC)(2)) or a selective inhibitor for inducible nitric oxide synthase (iNOS), S, S'-(4-phenylene-bis(1,2-ethanedinyl))bis-isothiourea (1,4-PB-ITU). Mother rats at day 21 of lactation were injected simultaneously with diethyldithiocarbamate intraperitoneally and Fe2+-citrate subcutaneously to form Fe(DETC)(2), in vivo, and then irradiated with 1.5 Gy gamma-rays immediately after the injection. An additional injection of chemicals followed twice at 8 and 24 h after the irradiation in the same manner. Both control and treated rats were then implanted with diethylstilbestrol pellets as a tumor promoter. The mammary tumor incidence in the experimental group was significantly reduced to one-fourth of that in the irradiated-alone group as the control. On the other hand, when mother rats took drinking water containing 0.005% 1,4-PB-ITU for 6 days from 3 days prior to irradiation at day 21 of lactation, a low tumor incidence in the iNOS inhibitor-treated groups was observed in the 1-year period. This report is the first to show that the NO derived from iNOS is an important radical for radiation-induced initiation of tumorigenesis of mammary glands in rats. (C) 2002 Elsevier Science (USA). All rights reserved.