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Inhibitory Effects Of Natural Phenolic Acids On DNA Damage

Posted on:2011-09-01Degree:MasterType:Thesis
Country:ChinaCandidate:L L TianFull Text:PDF
GTID:2154330338981287Subject:Pharmaceutical Engineering
Abstract/Summary:PDF Full Text Request
Hydroxyl radical and peroxyl radical, are important oxygen radicals generated in cells, and can lead to severe DNA damages, such as DNA strand breakage, base modification, base mutation. DNA damage induced by chemical carcinogens EB can lead to severe mutation. Free radicals and other kinds of chemical carcinogenses play an important role in the induction and development of cancer. Phenolic acids, are naturally occurring reactitive species, and exhibite many pharmacological activities, including anti-inflammatory, antioxidation, anti-aging, anticancer.The inhibition property of DNA damage induced by hydroxyl radical and peroxyl radical by natural phenolic acids was detected, comparing to the antioxidation of trolox. The antioxidative activity-structure relationship was analyzed. UV spectra property of phenolic acid after incubated with hydroxyl radical and peroxyl radical was also detected respectively. The fluorescence quenching property of EB-DNA by phenolic acids was detected, and the mechanism was also analyzed. Interfering effects of phenolic acids and EB on circular dichroism spectra of DNA ware measured, and the interaction mechanism between phenolic acid and DNA was also analyzed.Phenolic acids showed high antioxidation activity on the inhibition of DNA damage induced by hydroxyl radical and peroxyl radical. The structure-activity relationship showed that compounds with o-trihydroxy or o-dihydroxy group had strong antioxidation; the substitution of hydroxyl group by methoxy group could lead to low antioxidation activity, the antioxidation activity of compounds with side chain -CH=CHCOOH was strong, for the conjugative effect between double bond and benzene ring.The fluorescence spectra showed that phenolic acids had high fluorescence quenching property on EB-DNA system, and static quenching mode played an important role in the fluorescence quenching mechanism. Phenolic acid inhibited the insertion of EB into DNA base pairs by the formation of phenolic acids-DNA compounds. The circular dichroism spectra showed that the conformation changes of DNA induced by phenolic acids and EB were different; phenolic acids reduced the conformation changes of DNA induced by EB. The interaction between phenolic acids and DNA belonged to groove combination by noncovalent bond between phenolic hydroxyl group or carboxyl group and negative ions in DNA. Therefore, phenolic acids could protect DNA from free radical and carcinogens damages.This study revealed the DNA protection activity of phenolic acids on molecular level, and the research provided some information for screening more natural active components.
Keywords/Search Tags:hydroxyl radical, peroxyl radical, phenolic acid, fluorescence spectrum, circular dichroism spectra, DNA conformation
PDF Full Text Request
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