Mechanisms of Chemically Induced Photosensitivity

National Institute Of Environmental Health Sciences

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Abstract

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.