Bomgaars L, Gunawardena S, Kelley S E, Ramu A
Texas Children's Cancer Center, Baylor College of Medicine, Houston 77030, USA.
Cancer Chemother Pharmacol. 1997;40(6):506-12. doi: 10.1007/s002800050694.
Irradiation of doxorubicin (DOX) dissolved in RPMI medium 1640 by long ultraviolet (UVA) light results in a rapid decline in the cytotoxic activity of the drug. The present study was designed to sort out which component(s) of this medium are associated with the UVA inactivation of DOX.
The effects of UVA irradiation of DOX in solutions of various compositions were evaluated by measuring the changes in the drug growth inhibitory activity in P388 cells and in the DOX absorbance spectrum.
Riboflavin seemed to be the major photosensitizing component in the medium and the effect was enhanced by the presence of histidine, methionine, tryptophan and tyrosine but not by other amino acids. The changes in DOX resulting from UVA irradiation in the presence of riboflavin, were not blocked by 1,4-diazabicyclo [2.2.2]octane (5 mM), superoxide dismutase (300 units/ml), catalase (150 units/ml) or sodium benzoate (50 mM). The effects of UVA light on doxorubicin could be prevented by excess ascorbic acid.
The effects of UVA on DOX are mediated by riboflavin. The photoexcited riboflavin apparently interacts directly with DOX rather than by first forming reactive oxygen species. The results suggest that the photoinactivation of DOX may involve an oxidation step. The mechanism by which certain amino acids facilitate the photoinactivation of DOX is not known. It is suggested that patient intake of riboflavin and exposure to the sun and fluorescent light could affect the outcome of anthracycline treatment.
用长波紫外线（UVA）照射溶解于RPMI 1640培养基中的阿霉素（DOX）会导致该药物的细胞毒性活性迅速下降。本研究旨在找出该培养基的哪些成分与DOX的UVA失活有关。
通过测量P388细胞中药物生长抑制活性的变化以及DOX吸收光谱的变化，评估UVA照射DOX在各种组成溶液中的效果。
核黄素似乎是培养基中的主要光敏成分，组氨酸、蛋氨酸、色氨酸和酪氨酸的存在会增强这种效果，而其他氨基酸则不会。在核黄素存在的情况下，UVA照射导致的DOX变化不受1,4 - 二氮杂双环[2.2.2]辛烷（5 mM）、超氧化物歧化酶（300单位/毫升）、过氧化氢酶（150单位/毫升）或苯甲酸钠（50 mM）的阻断。过量的抗坏血酸可以防止UVA光对阿霉素的影响。
UVA对DOX的影响是由核黄素介导的。光激发的核黄素显然直接与DOX相互作用，而不是先形成活性氧。结果表明，DOX的光失活可能涉及一个氧化步骤。某些氨基酸促进DOX光失活的机制尚不清楚。有人提出，患者摄入核黄素以及暴露于阳光和荧光下可能会影响蒽环类药物治疗的结果。
