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Combined exposure to multiple carcinogens enhances development of rat mammary cancers with characteristic gene expression.
https://repo.qst.go.jp/records/70827
https://repo.qst.go.jp/records/70827499b0db1-1aa4-4808-a3b5-72ddf9bdace1
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-07-18 | |||||
| タイトル | ||||||
| タイトル | Combined exposure to multiple carcinogens enhances development of rat mammary cancers with characteristic gene expression. | |||||
| 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 |
Imaoka, Tatsuhiko
× Imaoka, Tatsuhiko× Nishimura, Mayumi× Ishikawa, Kenichi× Yamashita, Satoshi× Ohmachi, Yasushi× Suzuki, Hideyuki× Daino, Kazuhiro× Ushijima, Toshikazu× Imai, Takashi× Shimada, Yoshiya× 今岡 達彦× 西村 まゆみ× 石川 顕一× 大町 康× 鈴木 秀之× 臺野 和広× 今井 高志× 島田 義也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Introduction: Although mixed exposure to multiple carcinogens is common in human environment, the mechanism of cooperative carcinogenesis by two or more agents is poorly understood. In the present study, we undertook experiments using the rat mammary carcinogenesis model to assess the synergistic effect of combined exposure to gamma rays and chemical carcinogens and potential underlying mechanisms. Materials and Methods: Female Sprague-Dawley rats at 7 weeks of age were irradiated with gamma rays (0, 0.5, 1 and 2 Gy); three days after irradiation, rats were subjected to single i.p. injection with 1-methyl-1-nitrosourea (MNU; 20 or 40 mg/kg) or 10 oral administrations with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP; 40 mg/kg over two weeks), or left without chemical treatment. Tumors were examined pathologically after autopsy at 50 weeks of age. H-ras gene mutation was assessed by a restriction fragment length assay. Microarrays were used to search for genes characteristically expressed in combined exposure-induced carcinomas, followed by quantitative RT-PCR analysis incorporating additional tumors. Results: Incidence of mammary carcinoma increased linearly as a function of radiation dose in the absence of chemicals. Administration of chemical carcinogens resulted in additive increase in cancer incidence. Significantly high (78%) prevalence of H-ras mutation was observed among carcinomas of rats exposed to gamma rays (1 Gy) plus MNU (40 mg/kg) as compared to rats exposed to either gamma rays (0%) or MNU (54%) only. Microarray and quantitative RT-PCR analyses identified characteristic gene expressions in carcinoma induced by combined exposures as compared to those induced by single carcinogens. For example, high expression of serum/glucocorticoid-regulated kinase (Sgk) was associated with carcinomas induced by gamma rays (1 Gy) plus MNU (40 mg/kg) harboring H-ras mutation, whereas matrix metalloproteinase 17 was highly expressed in those without the mutation. Sgk may be induced synergistically by radiation effects (e.g., oxidative stress, nitric oxide and TGFbeta) and H-ras mutation and enhance proliferation of cancer cells. Carcinomas induced by gamma rays (1 Gy) plus PhIP contained abundant transcript of the transcription factor Lef1, which may activate Wnt-responsive genes and stimulate cancer progression. Conclusion: Interaction of oncogenic mechanisms at the molecular level may underlie the combined effect of multiple carcinogens on rat mammary carcinogenesis. |
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| 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 | The 22nd Biennial Congress of the European Association for Cancer Research | |||||
| 発表年月日 | ||||||
| 日付 | 2012-07-10 | |||||
| 日付タイプ | Issued | |||||
