2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potentiates nitrosation of a heterocyclic amine carcinogen by nitric oxide.
2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potentiates nitrosation of a heterocyclic amine carcinogen by nitric oxide.
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2-(4-羧基苯基)-4,4,5,5-四甲基咪唑啉-1-氧基-3-氧化物可增强杂环胺致癌物被一氧化氮的亚硝化作用。
DOI：
10.1016/j.lfs.2006.10.010
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发表时间：
2007
期刊：
影响因子：
6.1
通讯作者：
Zenser,TerryV
中科院分区：
文献类型：
--
作者：
Lakshmi,VijayaM;Zenser,TerryV
虽然亚硝化在致癌过程中起着重要的作用，但通过多种途径介导该反应的活性氮氧物质（RNOS）尚未确定。杂环胺致癌物2-氨基-3-甲基咪唑并[4，5-f]喹啉（IQ）被用作研究RNOS和增强一氧化氮（NO）介导的亚硝化作用的途径的目标。以2-（4-羧基苯基）-4，4，5，5-四甲基咪唑啉-1-氧基-3-氧化物（CPTIO）为催化剂，研究了NO2对亚硝化反应的促进作用。通过HPLC监测IQ亚硝化产物2-亚硝基氨基-3-甲基咪唑并[4，5-f]喹啉（14 C-N-NO-IQ）。精胺NONOate（2.4 μM NO/min）产生的NO自动氧化7.5 min，未将10 μ M 14 C-IQ转化为N-NO-IQ。然而，15 μM CPTIO的存在导致3 μM N-NO-IQ形成。CPTIO的增强作用发生在低和高NO流量（0.075至1.2 μM/min）以及IQ与CPTIO比值为0.5至10的范围内。N-NO-IQ形成的显著部分对叠氮化物（10 mM）抑制不敏感，表明氧化亚硝基化。NADH（0.02 mM）没有改变亚硝化的自氧化，但有效地抑制增强CPTIO。抗坏血酸（0.2 mM）和5，5-二甲基-1-吡咯啉N-氧化物（30 mM）抑制亚硝化与或没有CPTIO，而超氧化物歧化酶没有抑制作用。由CPTIO产生的RNOS对IQ的亲和力是由自氧化产生的RNOS的27倍。结果与NO2或RNOS如NO2增强IQ氧化亚硝基化一致。在低和高NO通量下发生的亚硝化都可能导致致癌作用。
Although nitrosation plays an important role in initiation of carcinogenesis, the reactive nitrogen oxygen species (RNOS) mediating this reaction by multiple pathways have not been determined. The heterocyclic amine carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was used as a target to investigate RNOS and pathways for potentiation of nitric oxide (NO)-mediated nitrosation. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO) oxidizes NO to NO2and was used as a tool to investigate NO2potentiation of nitrosation. The IQ nitrosation product, 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (14C–N–NO–IQ), was monitored by HPLC. Autoxidation of NO, generated by spermine NONOate (2.4 μM NO/min) for 7.5 min, did not convert 10 μM14C–IQ to N–NO–IQ. However, the presence of 15 μM CPTIO resulted in 3 μM N–NO–IQ formation. Potentiation by CPTIO occurred at low and high fluxes of NO, 0.075 to 1.2 μM/min, and over a range of IQ to CPTIO ratios of 0.5 to 10. A significant portion of N–NO–IQ formation was insensitive to azide (10 mM) inhibition, suggesting oxidative nitrosylation. NADH (0.02 mM) did not alter nitrosation by autoxidation, but effectively inhibited potentiation by CPTIO. Ascorbic acid (0.2 mM) and 5,5-dimethyl-1-pyrroline N-oxide (30 mM) inhibited nitrosation with or without CPTIO, while superoxide dismutase was not inhibitory. The RNOS produced by CPTIO had a 27-fold greater affinity for IQ than those produced by autoxidation. Results are consistent with NO2or a RNOS like NO2potentiating IQ oxidative nitrosylation. Nitrosation occurring at both low and high fluxes of NO can contribute to carcinogenesis.