Laval F, Wink D A
Groupe Radiochimie de l'ADN, U 247 INSERM, Institut Gustave-Roussy, Villejuif, France.
Carcinogenesis. 1994 Mar;15(3):443-7. doi: 10.1093/carcin/15.3.443.
Nitric oxide (NO) has been shown to be involved in a number of physiological processes. In the presence of oxygen, this reactive diatomic molecule is capable of generating reactive nitrogen oxide species (NOx) which possess both nitrosating and oxidizing ability for various substrates, including certain biological macromolecules. This report shows the inhibition of the DNA repair protein, O6-methylguanine-DNA-methyltransferase, by Et2N[N(O)NO]Na (DEA/NO), a compound which decomposes with concurrent release of NO. The inhibition of the purified transferase activity by NO was dose- and time-dependent and the extent of inhibition by DEA/NO corresponded to the total quantity of NO released. This inhibitory effect by NO was also demonstrated to be reversible over time. The reaction of the NO released from DEA/NO with cysteine under aerobic conditions resulted in the formation of an S-nitrosothiol adduct, suggesting that a similar adduct could be responsible for the inactivation.
一氧化氮（NO）已被证明参与多种生理过程。在有氧存在的情况下，这种具有反应活性的双原子分子能够生成活性氮氧化物（NOx），这些物质对包括某些生物大分子在内的各种底物具有亚硝化和氧化能力。本报告显示，Et2N[N(O)NO]Na（DEA/NO，一种分解时会同时释放NO的化合物）对DNA修复蛋白O6-甲基鸟嘌呤-DNA甲基转移酶具有抑制作用。NO对纯化的转移酶活性的抑制作用呈剂量和时间依赖性，DEA/NO的抑制程度与释放的NO总量相对应。随着时间的推移，NO的这种抑制作用也被证明是可逆 的。在有氧条件下，DEA/NO释放的NO与半胱氨酸反应生成了S-亚硝基硫醇加合物，这表明类似的加合物可能是导致失活的原因。
