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Role of mutagenic 8-nitroguanine in estrogen-dependent radiation-induced mammary tumorigenesis of rats

https://repo.qst.go.jp/records/70887
https://repo.qst.go.jp/records/70887
77e0b5cc-709d-4cd1-a064-d40c2b613a7c
Item type 会議発表用資料 / Presentation(1)
公開日 2012-09-12
タイトル
タイトル Role of mutagenic 8-nitroguanine in estrogen-dependent radiation-induced mammary tumorigenesis of rats
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_c94f
資源タイプ conference object
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Kawanishi, Shosuke

× Kawanishi, Shosuke

WEKO 696582

Kawanishi, Shosuke

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Onoda, Makoto

× Onoda, Makoto

WEKO 696583

Onoda, Makoto

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Inano, Hiroshi

× Inano, Hiroshi

WEKO 696584

Inano, Hiroshi

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Ohnishi, Shiho

× Ohnishi, Shiho

WEKO 696585

Ohnishi, Shiho

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Murata, Mariko

× Murata, Mariko

WEKO 696586

Murata, Mariko

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et.al

× et.al

WEKO 696587

et.al

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小野田 眞

× 小野田 眞

WEKO 696588

en 小野田 眞

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稲野 宏志

× 稲野 宏志

WEKO 696589

en 稲野 宏志

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抄録
内容記述タイプ Abstract
内容記述 Radiation of female rats during lactation results in a higher incidence of mammary tumors. Inano and Onoda have reported that nitric oxide (NO) participates in the formation of estrogen-dependent mammary adenocarcinomas following radiation. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are considered to play important roles in carcinogenesis through oxidative and nitrative DNA damage. Kawanishi and colleagues have demonstrated the formation of 8-nitroguanine as a potential biomarker to evaluate the risk of inflammation-related carcinogenesis in humans and animals. 8-Nitroguanine is a nitrative DNA lesion caused by RNS, which can lead to mutation via generating apurinic site in DNA. In this study, we examined 8-nitroguanine formation in mammary tumorigenesis induced by radiation with steroid analogue in rats.
Wistar-MS rats were exposed to whole-body irradiation with gamma-rays (1.5 Gy) at day 21 of lactation, and then implanted with a pellet of diethylstilbestrol (DES, a tumor promoter) in the interscapular area at one month after irradiation. After 1 year for the development of mammary tumors, mammary tissues were obtained, fixed with formalin, embedded in paraffin, and followed by immunohistochemical analyses. Wistar-MS rats were primed by implantation with 17beta-estradiol (E2) pellet. After 2 weeks of priming the mammary glands were isolated, diced into 5-mm cubes and cultured with an appropriate medium for 24h. The cultured mammary glands were then irradiated with X-rays (0, 5, 10, 20 Gy), incubated for additional 20h, fixed with formalin, and analyzed as described above.
In the current study the formation of 8-nitroguanine was clearly obserbed in fibroadenomas and adenocarcinomas developed in rats treated with gamma-rays and DES. This suggests that nitrative DNA damage was induced and accumulated in rat mammary glands by radiation and DES. The formation of 8-nitroguanine were also detected in mammary glands irradiated in the culture after isolation from E2-treated rats. Interestingly, the immunoreactivity to 8-nitroguanine appeared to increase in dose-dependent manner of X-rays. In conclusion, iNOS-derived NO may play a role in the formation of estrogen-dependent mammary adenocarcinomas via 8-nitroguanine formation following radiation.
会議概要(会議名, 開催地, 会期, 主催者等)
内容記述タイプ Other
内容記述 14th International Congress of Radiation Research
発表年月日
日付 2011-09-01
日付タイプ Issued
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