Photosensitization by drugs

Certain drugs are known to elicit photosensitivity side effects. A satisfac tory understanding of the involved mechanistic aspects is necessary to anti cipate the photosensitizing potential. We have used tiaprofenic acid (TPA), a photosensitizing nonsteroidal antiinflammatory drug, to illustrate the m ethodology followed to address this problem. After studying the photophysic al and photochemical properties of TPA- the attention has been directed tow ards the reactivity of its lowest lying pi-pi* triplet with biomolecules. P hotosensitized lipid peroxidation occurs by a mixed type I(radicals) and ty pe II (singlet oxygen) mechanism. In the case of proteins. the photosensiti zed reactions include Tyr, Trp, and His photodegradation. protein-protein p hotocrosslinking and drug-protein photobinding. This involves direct quench ing of the drug triplet by the amino acid residues (Tyr and Trp) or by oxyg en. followed by singlet oxygen oxidation (His and Trp). With DNA, the studi es have included comet assay, induction of single-strand breaks in supercoi led DNA, and reaction with 2'-deoxyguanosine and thymidine. Product studies , together with time-resolved measurements, have shown that the fastest rea ction occurs with purine bases, by a mechanism involving both radical and s inglet oxygen processes. The employed methodology can be of general use to investigate the mechanistic aspects of photosensitization by drugs.