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Prevention of genomic instability by...
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Prevention of genomic instability by the dietary antimutagens genistein and lycopene.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Prevention of genomic instability by the dietary antimutagens genistein and lycopene./
作者:
Batoon, Audrey King.
面頁冊數:
201 p.
附註:
Adviser: Catherine B. Klein.
Contained By:
Dissertation Abstracts International69-05B.
標題:
Health Sciences, Nutrition. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3312916
ISBN:
9780549621270
Prevention of genomic instability by the dietary antimutagens genistein and lycopene.
Batoon, Audrey King.
Prevention of genomic instability by the dietary antimutagens genistein and lycopene.
- 201 p.
Adviser: Catherine B. Klein.
Thesis (Ph.D.)--New York University, 2008.
This thesis investigated the activities and mechanisms that dietary antimutagens reduce the elevated spontaneous mutagenesis levels in human breast cancer cells. The putative chemopreventive agents, genistein (3.125 muM, 24 hrs) or lycopene (2 muM, 24 hrs) reduced the elevated spontaneous HPRT mutant fractions intrinsic in the breast tumor cells MCF-7 (ERalpha+), MDA-MB-468 (ERalpha-), and BT-474 (ERalpha+/-) by 31% to 49%. Coordinately, all three cell lines exhibited reduced frequencies of micronuclei. Analysis of microsatellite instability (MSI) showed that prevention of MSI at the anonymous chromosome 17 G29672 MSI marker was informative for 1-week exposures to genistein or lycopene in MCF-7 single cell clones. However, this MSI marker was not informative for MDA-MB-468 and BT-474 cells. Previously, we reported that MCF10A non-tumor breast cells pre-treated with genistein (3.125 muM and 12.5 muM, 24 hrs) or lycopene (2 muM and 20 muM, 24 hrs) prior to a low dose X-ray (0.75 Gy) exposure were protected against X-ray-induced aneuploidy. The dietarily-relevant and antimutagenic concentrations of genistein (3.125 muM, 24 hrs) or lycopene (2 muM, 24 hrs) also shows protection against X-ray induced MSI (G29672) in the non-tumor MCF10A cells. Apoptosis was investigated by flow cytometry and TUNEL assays as a possible antimuatagenic mechanism, but was not observed at the very low dietary-relevant concentrations of genistein or lycopene utilized in this study. At higher concentrations of genistein (50 muM, 48 hrs), a G2/M cell cycle shift was observed. To explore further mechanisms we found that both genistein (3.125 muM, 48 hr resupplementation for 1 week) and lycopene (2 muM, 1 week) modulate the methylation patterns of the GSTP1 tumor suppressor gene in MDA-MB-468 cells. RT-PCR studies confirm a lack of GSTP1 expression in untreated MDA-MB-468, with restoration of GSTP1 expression after genistein treatment (3.125 muM, 48 hr resupplementation for 1 week) or lycopene treatment (2 muM, 1 week). Lycopene (2 muM, 2 weeks) also modulated the methylation patterns of RARbeta2 in MCF10A cells. In summary, genistein and lycopene, at low dietarily relevant doses, attenuate the ongoing genomic instability present in tumor cells, possibly mitigating further tumor progression and metastasis.
ISBN: 9780549621270Subjects--Topical Terms:
1017801
Health Sciences, Nutrition.
Prevention of genomic instability by the dietary antimutagens genistein and lycopene.
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