Mechanisms of Chemically Induced Photosensitivity

我们已经证明，非甾体雄激素受体（AR）配体TDPQ，荧光化合物，是光化学活性和光细胞毒性培养的人前列腺癌细胞，可能是由于其单线态氧产量约7%。 TDPQ AR调节活性与其光细胞毒性潜力的组合使其成为一种有前途的光敏剂，其具有在光动力治疗期间选择性靶向AR阳性恶性细胞的吸引力潜力。 我们已经证明，拉莫三嗪，一种抗惊厥和抗抑郁药上市lamictal，是一种温和的光敏剂1 O2，并易于光脱氯，特别是在还原环境中。研究表明，在腐殖酸（HA）水溶液中，阻燃剂3，3，5，5-四溴双酚A（TBBPA）被单线态氧（1 O2）氧化。我们的研究结果是相关的环境TBBPA在水生系统中的降解，因为他们建议一种类型的产品，可能会产生，积累，并对水生生物系统和人类构成潜在的危害。当对大鼠给予TBBPA时，产生自由基，可能导致观察到的TBBPA对大鼠的肝毒性。 我们已经评估了饮食褪黑激素对视网膜光感受器的潜在毒性，发现在雄性和雌性无色素Fischer大鼠中，当在夜间或白天施用褪黑激素，随后暴露于高强度照明（1000-1500 lx; HII）2小时时，褪黑激素施用增加了光感受器细胞死亡的程度。长期暴露于自然光或人造光以及同时摄入褪黑激素可能潜在地导致老化视网膜中感光细胞的显著损失。 我们检查了用于诱导黄斑变性A2 E的假定发色团，发现蓝光氧化A2 E，然后显著损伤人视网膜色素上皮（RPE）细胞，尽管A2 E本身没有光毒性。我们发现氟喹啉，特别是用于对抗炭疽生物恐怖主义的环丙沙星，对透镜晶体蛋白具有光毒性。 我们还开发了一种简单实用的方法，用于测量单个光敏剂的光敏化指数，以比较不同家庭和办公室光源的潜在有害影响。

We have demonstrated that the non-steroidal androgen receptor (AR) ligand TDPQ, a fluorescent compound, is photochemically active and photocytotoxic to human prostate cancer cells in culture, probably due to its singlet oxygen production yield of about 7%. The combination of TDPQs AR modulating activity with its photocytotoxic potential makes it a promising photosensitizer that has the attractive potential to selectively target AR-positive malignant cells during photodynamic therapy. We have demonstrated that lamotrigine, an anticonvulsant and antidepressant drug marketed as lamictal, is a moderate photosensitizer of 1O2, and is prone to photo-dechlorination, especially in a reducing environment. We showed that the flame retardant 3,3,5,5-tetrabromobisphenol A (TBBPA) is oxidized by singlet oxygen (1O2) by the irradiation of humic acid (HA) in aqueous solutions. Our results are relevant to environmental TBBPA degradation in aquatic systems, as they suggest a type of product that may be produced, accumulate, and pose a potential hazard for both aquatic bio-systems and humans. When TBBPA was administered to rats, free radicals were produced, possibly contributing to the observed hepatotoxicity of TBBPA in rats. We have evaluated the potential toxicity of dietary melatonin on retinal photoreceptors, finding that in male and female non-pigmented Fischer rats, melatonin administration increased the degree of photoreceptor cell death when administered either at night or during the day when followed by exposure to high intensity illumination (1000-1500 lx; HII) for 2 h. Chronic exposure to natural or artificial light and simultaneous intake of melatonin may potentially contribute to a significant loss of photoreceptor cells in the aging retina. We examined the putative chromophore for the induction of macular degeneration A2E, finding that blue light oxidizes A2E, which then significantly damages human retinal pigment epithelium (RPE) cells, although A2E itself is not phototoxic. We found that fluoroquinolines and particularly Cipro, which is used against anthrax bioterrorism, are phototoxic to lens crystalline proteins. We have also developed a simple and practical method for measuring an index of photosensitization for an individual photosensitizer in order to compare the potential for harmful effects from different household and office light sources.