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Benzo ( a ) pyrene 대사물질들의 DNA 에 대한 Adduct 형성 억제에 미치는 Panaxydol 의 효과
Inhibition of the Formation of Adducts Between Metabolites of Benzo ( a ) pyrene and DNA by Panaxydol in vivo and in vitro
박진규(Jin Kyu Park),김신일(Shin Il Kim)
UCI I410-ECN-0102-2009-480-004950252
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PAH계 화합물들의 Bay region diol epoxide들의 target tissue에 대한 결합은 암유발과 관련되어 있다. 본 논문에서는 ICR mice의 간에서의 BP-DNA-adduct 생성에 미치는 polyacetylene 화합물인 panaxynol과 panaxydol의 효과를 조사하였다. Panaxynol과 panaxydol을 전처리한 ICR mice의 간 마이크로좀을 포함하는 incubation system은 calf thymus DNA에 대한 BP binding을 뚜렷이 감소시켰다. [^3H]-BP(300μCi/21nmoles/0.1㎖ DMSO, i.v.)를 mice에 주사 후 24시간 후에 간 DNA에서의 방사능을 측정하였다. HPLC에 의해 cochromatography 한 두개의 standard marker (acetophenone, bytirophenone)들 사이에 나타나는 DNA adduct 들을 잠정적으로 확인한 결과 (-)BP-7,8-diol로 부터 생성되는 major adduct인 (+)BP-diol epoxide I:dGuo adduct (peakII)는 대조군보다 약 22% 감소된 반면에 minor adduct인 (-) BP-diol epoxide I: dGuo adduct(peak III)는 대조군의 69%로 감소되었다. 그리고 (+) BP-7,8-diol로부터 생성되는 minor adduct인 BP-diol epoxide II:Guo adduct(peak IV)는 대조군의 58%로 감소되었다. 이러한 결과는 panaxydol이 (±) BP-7,8-diol로부터 일반적으로 생성되는 adduct들 중 major 보다는 minor adduct들의 생성에 더 많이 관여했음을 보여준다.

The binding of bay region diol-epoxides of polycyclic aromatic hydrocarbons (PAHs)to target tissue DNA is thought to be essential for the initiation of cancer by these compounds. In this study we investigated the effect of polyacetylenes such as panaxynol and panaxydol on the formation of berzo(a)pyrene(BP)-metabolite-DNA adduct in the liver of ICR mice. Treatment of mice by i.p. administration of polyacetylenes produced a marked reduction in BP metabolite binding to DNA in vitro. Following i.v. administration of [^3H]BP(300μCi/21 nmoles/0.1㎖ DMSO) to mice, radioactivity was detected in the DNA of the liver in vivo. The result of tentative identification of the 4 peaks between the two standard makers for high pressure liquid chromatography showed that the peaks. Ⅰ,Ⅱ,Ⅲ,and Ⅳ were BP-phenol oxile-DNA adduct (or BP-diol-epoxide-dCyt. adduct), (-) BP-diolepoxide I:d GuO adduct, (+) BP-diol-epoxide i: dGuo adduct, and BP-diol-epoxide II:dGuO adduct, respectively. The minor adduct, (-) BP-diol epoxide I: dGuo was reduced to 69% of the amount of the control, while the major adduct, (+) BP-diolepoxide I:dGuO(peak II) which was produced from (-) BP-7,8-diol was reduced to 78% of that of the control. The amount of the minor adduct, BP-diol-epoxide Ⅱ:dGuo adduct(peakⅣ) which formed from (+) BP-7,8-diol was 58% of the control. These results show that the panaxydol is more related to inhibition of the formation of the minor adducts than of the major adducts, which were generally produced from (±)BP-7,8-dihydro-diols.

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