Artuso T, Bernadou J, Meunier B, Paillous N
Laboratoire des IMRCP, UA 470 du CNRS, Université Paul Sabatier, Toulouse, France.
Biochem Pharmacol. 1990 Feb 1;39(3):407-13. doi: 10.1016/0006-2952(90)90044-l.
Benoxaprofen, a non steroidal antiinflammatory drug is known to be highly phototoxic. Upon irradiation at 300 nm, benoxaprofen is shown to enhance the cleavage of phi X 174 DNA in buffered aqueous solution (pH 7.4). A linear relationship between the number of single strand breaks and the irradiation time is found. In deaerated solutions, these breaks are three times greater in the presence than in the absence of benoxaprofen. In both cases the rate of cleavage decreases in the presence of air. The rate of DNA damage increases with the drug per base pair ratio up to approximatively 0.2 and then decreases at higher ratios. Other NSAIDs, naproxen, ketoprofen, diflunisal, sulindac and indomethacin have been tested as photocleavers of DNA by using the same experimental conditions. A comparison of the efficiency of cleavage of all these drugs (including BNP) was obtained at drug concentrations such that the light absorbance was the same. Benoxaprofen, naproxen, ketoprofen and diflunisal induce single strand breaks. Sulindac and indomethacin do not cause breaks, and they can in some conditions even act as screening agents. The most efficient of the series are naproxen and ketoprofen. In the presence of oxygen, at the same concentrations as above, the efficiency of benoxaprofen, ketoprofen and diflunisal is decreased while that of naproxen is increased. This suggests that all these compounds do not interact with DNA by the same mechanism. In the case of BNP, the mechanism of photoinduced DNA cleavage is discussed in detail. It is shown that the photoactive agent is the decarboxylated derivative of benoxaprofen, as the photodecarboxylation of benoxaprofen is much faster than the photocleavage of DNA.
苯氧布洛芬是一种非甾体抗炎药，已知具有高度光毒性。在300nm波长照射下，苯氧布洛芬在缓冲水溶液（pH 7.4）中能增强φX 174 DNA的切割。发现单链断裂数与照射时间呈线性关系。在脱氧溶液中，有苯氧布洛芬时的这些断裂比没有时大三倍。在两种情况下，有氧存在时切割速率均降低。DNA损伤速率随药物与碱基对的比例增加，直至约0.2，然后在更高比例时降低。其他非甾体抗炎药，如萘普生、酮洛芬、二氟尼柳、舒林酸和吲哚美辛，已在相同实验条件下作为DNA光切割剂进行了测试。在药物浓度使吸光度相同的情况下，对所有这些药物（包括苯氧布洛芬）的切割效率进行了比较。苯氧布洛芬、萘普生、酮洛芬和二氟尼柳诱导单链断裂。舒林酸和吲哚美辛不会导致断裂，在某些情况下它们甚至可以作为筛选剂。该系列中最有效的是萘普生和酮洛芬。在有氧存在下，在上述相同浓度下，苯氧布洛芬、酮洛芬和二氟尼柳的效率降低，而萘普生的效率增加。这表明所有这些化合物与DNA相互作用的机制不同。对于苯氧布洛芬，详细讨论了光诱导DNA切割的机制。结果表明，光活性剂是苯氧布洛芬的脱羧衍生物，因为苯氧布洛芬的光脱羧比DNA的光切割快得多。
