1.Evaluation of Dietary Soy Containing Phytoestrogens on the Hemostatic System in Postmenopausal Women 2.Analysis of Nickel Inhibiting Human MutSβismatch Repair Pathway
Date Issued
2008
Date
2008
Author(s)
Tsao, Wen-Ching
Abstract
Menopause is the cessation of a woman''s menstrual periods and usually occurs between ages 45 and 55. During menopause many women experience such symptoms as hot flashes, depression, anxiety, insomnia, fatigue, heart palpitations, and weight gain. Post menopausal hormone replacement therapy (HRT) could reduce menopausal syndrome. Physicians routinely prescribed estrogens for women who complained of hot flashes and other symptoms associated with menopause. Unfortunately, this medical practice greatly increased the chances for developing cancer, thrombophlebitis, strokes and heart attacks in many women. Recently, physicians are now aware of this danger and seeking safer and effective substitutes such as phytoestrogens in treating menopausal symptoms. However, it is not understood whether phytoestrogens may cause similar side effects as estrogen treatment. The purpose of this study is to evaluate thrombophlebitis related coagulation factors after phtoestrogens treatment.he subjects were volunteers from Osteoporosis Prevention Plan of National Taiwan University Hospital. One hundred healthy postmenopausal women without menopausal symptoms and hormone replacement therapy were enrolled in a randomized double-blind trial conducted over 12 months. The phtoestrogen used in this study was isoflavone. The blood were sampled before treatment, after 6 months and in the end of 12 months. Thrombophlebitis related coagulation factors of Factor VII, D-dimer, vWF Ag, Protein S, PAI-1 were analyzed in this study. Using Student''s t tests analysis, we found there were no significant differences of all five coagulation factors between the groups taking the placebo and isoflavone. Therefore, treatment of isoflavone did not show adverse effect to coagulation factors tested.ismatch repair (MMR) maintains genome stability by correction of DNA biosynthetic errors during the replication. Inactivation of MMR activity results in genetic instability, which is assumed to promote tumorigenesis. ickel (II) is a ubiquitous environmental and industrial contaminant. It is also a well-known human carcinogen causing respiratory cancers. Human cells treated with Ni(II) had been shown microsatellite instability of short tandem repeat contraction and expansion, a well-known signature of losing mismatch repair capability. The purpose of this study was to determine whether Nickel (II) may cause genetic instability by inhibiting human mismatch repair, specifically small nucleotide insertion/deletion repair related MutSβ pathway. e used a set of 4-nucleotide insertion/deletion heteroduplexes to examine the effect of nickel (II) on MutSβ mismatch repair pathway in human cells. We found that addition of nickel (II) significantly inhibits human mismatch repair and the inhibition appears to be dose dependent. However, the inhibition of mismatch repair is prevented by asparagine, suggesting that these residues are essential for the repair enzymes and are targeted by nickel (II). Using sulfhydryl containing chemicals, we have found that the inhibitory effect of Nickel (II) on the mismatch repair activity was overcome by addition of dithiothreitol but not β-mercaptoethanol. Our results provide strong evidence that nickel (II) can inhibit mismatch repair pathway in human cells, and this may constitute one of the important mechanisms of nickel (II)-induced human carcinogenesis.
Subjects
Phytoestrogens
Postmenopausal
Nickel
Human Mismatch repair
SDGs
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