抗肿瘤药物的光敏作用，4. 蒽吡唑对DNA中单链断裂的光敏形成

Photosensitization by antitumor agents, 4. Anthrapyrazole-photosensitized formation of single strand-breaks in DNA.

作者信息

Hartley J A, Reszka K, Lown J W

机构信息

Department of Chemistry, University of Alberta, Edmonton, Canada.

出版信息

Free Radic Biol Med. 1988;4(6):337-43. doi: 10.1016/0891-5849(88)90085-8.

DOI:10.1016/0891-5849(88)90085-8

PMID:3384343

Abstract

Single-strand breaks can be introduced into PM2 closed-circular DNA upon illumination with blue light, in the presence of the anthrapyrazole antitumor agent, compound 1. Damage is observed already after 1 min of blue light illumination, and is significantly enhanced by the presence of electron donors such as NADH, ascorbic acid or Fe(III)/EDTA complex. The photosensitizing properties were not observed for anthrapyrazole analogues with one or more hydroxyl substituents in the chromophore of the drug. The inhibitory effects of sodium azide, methanol, mannitol, SOD, and catalase suggest an oxygen-dependent mechanism of strand-break production, probably involving hydroxyl radicals. However, a second mechanism involving drug molecules bound to the DNA is also indicated under anoxic conditions in the presence of NADH.

摘要

在存在蒽吡唑抗肿瘤剂化合物1的情况下，用蓝光照射时，单链断裂可引入PM2闭环DNA中。蓝光照射1分钟后即可观察到损伤，并且电子供体如NADH、抗坏血酸或Fe(III)/EDTA复合物的存在会显著增强损伤。在药物发色团中具有一个或多个羟基取代基的蒽吡唑类似物未观察到光敏特性。叠氮化钠、甲醇、甘露醇、超氧化物歧化酶和过氧化氢酶的抑制作用表明链断裂产生的氧依赖性机制，可能涉及羟基自由基。然而，在缺氧条件下，在NADH存在的情况下，也表明存在涉及与DNA结合的药物分子的第二种机制。