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標題: 4-鄰位醌類衍生物誘發小牛胸腺DNA去鹼基核酸及單鏈斷裂生成之研究
作者: 林伯雄
關鍵字: 去鹼基核酸
出版社: 國立中興大學工學院;Airiti Press Inc.
摘要: 本研究之主知即在於應用生物性指標(biomarker)探討氯酚之鄰位?類化物,4-單氯烴?(4-chlorocatechol, 4-ClCAT)能否經由不斷氧化還原循環(redox cycle)進而生成活潑性氧(reactive oxygen species, ROS)對DNA造成破壞作用,包括去鹼基核酸(paurinic/apyridiminic, AP sites)及DNA單鏈斷裂(single strand break, SSB)進行測試。研究結果顯示,4-ClCAT於過渡性金屬銅Cu(II)存在之環境下能對小牛胸腺DNA同時誘發DNA SSB及AP sites之核酸損害作用。ROS移除劑,例如氫氧自由基移除劑DMSO(6%)、甲醇(6%),超氧自由基移除劑superoxide dismatase (SOD)對DNA SSB及AP sites,均無抑制作用,但過氧化氫酵素(catalase)具有抑制效應,顯示其中實際參與核酸損害作用之ROS分子為H2O2。同時,Cu(I)螫合劑,bathocuproine共同反應情形下,能抑制Cu(II)與4-ClCAT誘發的核酸損害作用,一結果顯示Cu(I)與活潑性氧分子中之H2O2可能為實際參與核酸損害作用之物種。此外,glutatione(GSH)亦可抑制 Cu(II)與4-ClCAT所誘發的DNA SSB及AP sites之生成,此一研究證據顯示,GSH可能是與4-ClCAT結合後中斷其氧化還原之環,終止ROS生成,進而抑制核酸損害作用,同時GSH亦有可能是直接與ROS反應,直接移除ROS,遠到保護DNA之作用。總結上述之實驗證據,如同對位?類化物,氯酚之鄰位?類物亦可經由不斷之氧化還原循環(redox cycle)生成H2O2,並對DNA造成氧化損害作用。
DNA damage induced by 4-chlorocatechol (4-ClCAT) was investigated using calf thymus DNA (ct-DNA) under physiological conditions. Results indicated that with the addition of transition metal copper (II) (20-100μM), parallel increases in DNA strand breaks and abasic (AP) sites were detected in ct-DNA exposed to 4-ClCAT(0.1-100μM) over the corresponding control. In the presence of both Cu(II) (20μM) and NADPH (100μM), 4-ClCAT induce a 100-fold increase in the number of AP sites at nanomolar concentration under physiological conditions. Further investigation indicated that the DNA damage induced by 4-ClCAT plus Cu(II) and NADPH was inhibited by the additons of catalase, copper(I)-specific chelator, and glutathione whereas superoxide dismutase and hydroyl radical scavengers were ineffective. These results suggest the involvement of Cu(I) and hydrogen peroxide in the induction of oxidative DNA damage by 4-ClCAT. In summary, these data demonstrate that similar to the para-quinonoid counterparts, chlorinated ortho-quinonoids are capable of inducing significant oxidative modifications in genomic DNA.
ISSN: 1017-4397
Appears in Collections:第13卷 第3期



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