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药物光敏化的分子机制。IX. 无机离子对萘普生光敏化DNA裂解的影响。

Molecular mechanism of drug photosensitization. IX. Effect of inorganic ions on DNA cleavage photosensitized by naproxen.

作者信息

De Guidi G, Giuffrida S, Condorelli G, Costanzo L L, Miano P, Sortino S

机构信息

Dipartimento di Scienze Chimiche, Università di Catania, Italy.

出版信息

Photochem Photobiol. 1996 Apr;63(4):455-62. doi: 10.1111/j.1751-1097.1996.tb03069.x.

DOI:10.1111/j.1751-1097.1996.tb03069.x
PMID:8934762
Abstract

Photocleavage of DNA induced by naproxen and the correlated protective effect by some inorganic ions have been considered. The presence of a DNA complex is suggested and only associated naproxen seems to be responsible for the cleavage, for which the quantum yield of single strand breaks was calculated. The inorganic ions I-, Mn2+, Co2+ and Cu2+ decrease naproxen-photoinduced DNA cleavage. Iodide acts by a heavy atom mechanism, thus inhibiting naproxen photolysis and decreasing the amount of free radicals responsible for the photocleavage both in aerobic and anaerobic conditions. Metallic ions protect only within a range of concentrations, as for higher amounts damaging processes are observed. The protective efficiency of cations decreases with the increase of free drug concentration in the bulk of the solution, due to their involvement in the scavenging of naproxen radicals generated by photolysis of the free drug. In the presence of EDTA the cations show a better protective action. The most likely hypothesis is an inhibiting effect on the damaging processes via a redox cycle. The different behaviors of copper and of the two other cations can be justified by the influence of redox potentials of free and complexed metals and by the superoxide dismutase-like activity of copper.

摘要

已对萘普生诱导的DNA光裂解以及一些无机离子的相关保护作用进行了研究。有人提出存在一种DNA复合物,且似乎只有结合的萘普生会导致裂解,并计算了单链断裂的量子产率。无机离子I⁻、Mn²⁺、Co²⁺和Cu²⁺会减少萘普生光诱导的DNA裂解。碘离子通过重原子机制起作用,从而在有氧和无氧条件下抑制萘普生的光解,并减少负责光裂解的自由基数量。金属离子仅在一定浓度范围内起保护作用,因为当浓度较高时会观察到损伤过程。由于阳离子参与清除由游离药物光解产生的萘普生自由基,随着溶液主体中游离药物浓度的增加,阳离子的保护效率会降低。在存在乙二胺四乙酸(EDTA)的情况下,阳离子表现出更好的保护作用。最有可能的假设是通过氧化还原循环对损伤过程产生抑制作用。铜与其他两种阳离子的不同行为可以通过游离和络合金属的氧化还原电位的影响以及铜的超氧化物歧化酶样活性来解释。

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