Identification of DNA adducts in animals and breast cancer patients treated with tamoxifen
| Project/Area Number |
10671119
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
UMEMOTO Atsushi Second Department of Surgery, School of Medicine, The University of Tokushima, MD, Ph.D. Assistant Professor, 医学部・附属病院, 講師 (60185072)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUWA Masato Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Chief Investigator, 研究員
KOMAKI Kansei Second Department of Surgery, School of Medicine, The University of Tokushima, MD, Ph.D. Assistant Professor, 医学部・附属病院, 講師 (60215382)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
|
|---|
| Keywords | tamoxifen / α-(NィイD12ィエD1-deoxyguanosinyl)tamoxifen N-oxide / DNA adduct / ィイD132ィエD1P-postlabeling / endometrial cancer / ^<32>P-ポストラベル法 / ヒト白血球 / 発癌 / ^<32>p postlabeling |
|---|
| Research Abstract |
It is known that a long term treatment of tamoxifen for the breast cancer patients increases the incidence of endometrial cancer. The cause of this is assumed to be formation of DNA adducts by tamoxifen. In last year, we synthesized α-acetoxytamoxifen and α-acetoxytamoxifen N-oxide as activated forms, and obtained DNA adducts by reacting them with DNA and 2'-deoxyguanosine. These were identified as each four stereoisomers of α-(NィイD12ィエD1-deoxyguanosinyl)tamoxifen and α-(NィイD12ィエD1-deoxyguanosinyl) tamoxifen N-oxide by mass spectroscopy and nuclear magnetic resonance spectroscopy. In this year, we analyzed the liver samples of rats and mice treated with tamoxifen by ィイD132ィエD1P-postlabeling and m)LC using the above authentic adducts, and succeeded to detect these two types of tamoxifen-DNA adducts. In both animals, trans form of α-(NィイD12ィエD1-deoxyguanosinyl)tamoxifen was a principal DNA adduct that accounted for about 50% of the total DNA adduct level. In the mouse liver, trans form of α-(NィイD12ィエD1-deoxyguanosinyl)tamoxifen N-oxide was accounted for 7%, while in the rats it was for only 0.3%, This may be due to the higher activity of flavin-containing monooxygenase that catalyze N-oxidation of tamoxifen in the mice than rats. The DNA adducts of the patient's leucocytes was then analyzed. Trans-α-(NィイD12ィエD1-deoxyguanosinyl)tamoxifen was detected in the leucocyte DNA from the three patients among fifty breast cancer patients treated with tamoxifen. We are collecting endometrial DNA samples from the breast cancer patients treated with tamoxifen.
|
Report
(3 results)
Research Products
(10 results)
-
-
-
-
[Publications] Umemoto, A., Shibutani, S., Komaki, K., Suwa, M., Lin, C., Mimura, S. and Monden, Y.: "Identification of Tamoxifen-DNA adducts in white blood cells from breast cancer patients."Breast Cancer Res. Treat.. 50. 331 (1998)
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Publications] Umemoto, A., Shibutani, S., Suwa, M., Komaki, K., Lin, C., Mimura, S. and Monden, Y.: "Tamoxifen-DNA adducts in white blood cells obtained from breast cancer patients."In Marcos Moraes, Ricardo Brentani and Ruy Bevilacqua (ed.) 17th International Cancer Congress. Monduzzi Editore, Bologna Italy. 835-839 (1998)
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
