302. Exp Lung Res. 2002 Oct-Nov;28(

302. Exp Lung Res. 2002 Oct-Nov;28(7):577-90.

Assessment of the protective effect of amifostine on radiation-induced pulmonary
toxicity.

Vujaskovic Z(1), Feng QF, Rabbani ZN, Samulski TV, Anscher MS, Brizel DM.

Author information:
(1)Department of Radiation Oncology, Duke University Medical Center, Durham,
North Carolina 27710, USA. [e-mail]

The objective of this study was to assess the radioprotective effects of
amifostine in the rat model of radiation-induced lung injury using fractionated
doses of radiation, to determine whether amifostine given before irradiation
protects tumor from radiation cytotoxicity, and to determine whether changes in
plasma levels of transforming growth factor (TGF)-beta correlate with
radioprotective effect of amifostine. R3230 AC mammary adenocarcinoma was
transplanted on the right posterior chest wall of female Fisher-344 rats. Both
tumor-bearing and non-tumor-bearing animals were irradiated to the tumor or right
lung using 4 MV photons and fractionated dose of 35 Gy/5 fractions/5 days.
Animals with tumors and those without were randomized into 4 groups, respectively
(8 to 10 rats per group), to receive (1) radiation alone; (2) radiation +
amifostine; (3) amifostine alone; (4) sham radiation. Amifostine (150 mg/kg) was
given intraperitoneally 30 minutes before each fraction of irradiation. The tumor
size was measured twice a week. Breathing rate was assessed every 2 weeks.
TGF-beta levels in plasma were assessed monthly after treatment. Six months after
irradiation, animals were euthanized and lung tissue was processed for
hydroxyproline content analysis. A significant increase in breathing frequency
started 9 weeks after irradiation in animals that received radiation only. In the
radiation + amifostine group, there was both a delay and a significantly lower
peak in breathing frequency (P < .001). Hydroxyproline content was higher in the
radiation-alone group than in rats given amifostine prior to radiation (P < .05).
The TGF-beta levels in plasma showed an increase from 1 to 3 months after
radiation, peaking at 2 months in the rats with (2.80 +/- 0.23) or without (5.32
+/- 1.21) amifostine compared to sham irradiation. TGF-beta levels were
significantly lower at 1 to 3 months in rats receiving amifostine plus radiation
versus those receiving radiation alone. Tumor growth delay and regrowth rate
after radiation were not different between radiation-alone and radiation +
amifostine groups. This study confirms the protective effect of amifostine in
reducing radiation-induced pulmonary toxicity. No tumor protection was
demonstrated after fractionated radiotherapy. The reduction in pulmonary injury
with amifostine in paralleling lower plasma levels of TGF-beta, suggesting that
monitoring plasma levels of this cytokine may reflect the efficacy of an
intervention aimed at preventing radiation-induced lung injury.

PMID: 12396250 [PubMed - indexed for MEDLINE]

結果 (中文) 1:

302.exp 肺 res.2002年 10 月-11 月; 7:577-90。阿米福汀对辐射诱导肺的保护作用的评估毒性。Vujaskovic Z(1)，冯 QF，拉巴锌、 Samulski 电视，Anscher 女士，Brizel 德国马克。作者信息︰(1)辐射部肿瘤，杜克大学医学中心，达勒姆，北卡罗莱纳州 27710，美国。[e-mail]本研究的目的是评估的防护作用阿米福汀在大鼠模型的辐射引起的肺损伤使用分级剂量的辐射，以确定是否氨磷汀在辐照前给出从辐射的细胞毒性，并确定保护肿瘤是否变化转化生长因子 (TGF) 血浆水平-与 beta 相关阿米福汀的辐射防护作用。R3230 AC 乳腺腺癌是移植于雌性 Fisher 344 大鼠右后胸壁。两个荷瘤和非瘤动物被辐照向肿瘤或向右使用 4 MV 光子和 35 Gy/5 分数/5 天的分割的剂量的肺。动物肿瘤与那些没有随机分为 4 组分别（8 到 10 大鼠每个组），接收 (1) 辐射孤独;（2） 辐射 +阿米福汀;（3） 氨磷汀孤独;（4） 深水辐射。阿米福汀 （150 毫克/公斤） 是腹腔注射前每个分数照射 30 分钟。肿瘤尺寸测量了每周两次。呼吸速率被评估每隔 2 周。血浆中的 TGF-β 水平进行了评估每月后治疗。六个月后辐照，动物处死和肺组织被处理为羟脯氨酸含量分析。呼吸频率显著增加9 周收到辐射只的动物在照射后开始。在辐射 + 氨磷汀组没有延迟，显著降低在呼吸频率峰值 (P <.001 明显羟脯氨酸含量较高的辐射单独组比大鼠给予放射氨磷汀 (P <.05 明显血浆中 TGF-β 水平表明从 1 增加到 3 个月后辐射，在 2 个月 (+ /-0.23 2.80) 与大鼠的峰值或无 (5.32+ /-1.21) 氨磷汀相比假照射。TGF-β 水平显著降低大鼠接受氨磷汀加放疗 1 到 3 个月与那些单独的接收辐射。肿瘤生长延迟和再生速率辐射间没有不同辐射单后和辐射 +阿米福汀组。这项研究证实了氨磷汀中的保护作用降低辐射诱导的肺毒性。没有肿瘤保护了放疗后，表现出。在肺损伤减少与氨磷汀中并联低血浆的 TGF-β，暗示监测血浆水平这个细胞因子可能反映的疗效干预旨在防止辐射引起的肺损伤。PMID: 12396250 [PubMed - indexed for MEDLINE]

結果 (中文) 3:

302。口肺水库2002十月十一月；28（7）：577-90。对放射性肺氨磷汀的保护效果评价毒性。Vujaskovic Z（1），冯QF，Rabbani ZN，Anscher MS，这些萨穆尔斯基电视、DM。作者信息：（1）放疗科，杜克大学医学中心，美国，北卡罗莱纳27710，美国[e-mail]本研究的目的是评估防护作用在大鼠放射性肺损伤模型，采用分级的氨磷汀辐射剂量，以确定是否给予照射前氨磷汀保护肿瘤免受辐射的细胞毒性，并确定是否改变血浆转化生长因子-β（TGF-β1）与氨磷汀的辐射防护作用。乳腺癌是r3230交流移植在右后胸壁女费344大鼠。两肿瘤的轴承和非荷瘤动物被照射到肿瘤或右肺使用4个光子和分次剂量为35天/ 5分/ 5天。有肿瘤的动物和那些没有被随机分为4组，分别（每组8只，每组10只），单独接收（1）辐射；（2）辐射+氨磷汀；（3）氨磷汀单；（4）假辐射。氨磷汀（150毫克/公斤）为在照射前30分钟给予腹腔内各部分。肿瘤一周测量两次。每2周评估一个呼吸频率。TGFβ在血浆水平进行评估，每月治疗后。六个月后辐照，处死动物肺组织处理羟脯氨酸含量的分析。呼吸频率的一个显著增加开始9周后，在动物中，只接收辐射照射。在辐射+氨磷汀组，有一个延迟，显著降低呼吸频率峰值（P＜。001）。羟脯氨酸含量高的单纯照射组比放疗前给予氨磷汀组（P<0。05）。TGF-β水平的等离子显示从1个增加至3个月后辐射，峰值在2个月的大鼠（2.80 + / - 0.23）或无（5.32）+ / - 1.21）氨磷汀与假照。TGF-β水平明显低于1至3个月接受药物+照射大鼠和那些单独接受辐射的。肿瘤生长延迟和再生率辐射单独和辐射+之间没有什么不同氨磷汀组。这项研究证实了氨磷汀的保护作用降低辐射诱导的肺毒性。无肿瘤保护分次放疗后。肺损伤的减少在并联低血浆TGF-β氨磷汀，提示监测这种细胞因子的血浆水平可能反映了疗效的一个预防放射性肺损伤的干预措施。发表于：12396250 [ PubMed索引数据库]