title: The role of active oxygen (1O2 and O(2)) induced by crude coal tar and its ingredients used in photochemotherapy of skin diseases.
abstract: Crude coal tar (CCT) and certain photoreactive ingredients of CCT are photosensitizing agents used in the treatment of skin diseases (psoriasis, atopic eczema, etc.). Limited information is available in elucidating the mode of action of CCT in clearing psoriasis or causing skin photosensitization reactions. The production of singlet oxygen (1O2) and superoxide radicals (O(2) or HO2), the formation of interstrand cross-links (ICL) in DNA, and the skin photosensitization reaction caused by CCT or the ingredients present in tar preparations have been examined. Both type I (oxygen-independent) and type II (sensitized reactions requiring molecular oxygen) reactions are induced by CCT. Our data show that CCT and some of the photoreactive ingredients present in CCT produce 1O2, O(2), and ICL in DNA upon exposure to UVA radiation. Based on the equivalent concentration, the efficiency of various agents to produce 1O2 was of the following order: hematoporphyrin greater than phenanthridine greater than acridine greater than methylene blue greater than CCT greater than fluoranthrene greater than anthracene greater than pyrene greater than 8-methoxypsoralen greater than anthralin greater than chloroquine greater than anthralin dimer. The O(2) formation with CCT and its ingredients was also of the same order except for anthracene which was found to be a strong producer of O(2). The therapeutic effectiveness of CCT appears to be due to: (a) its cytotoxic effects, and (b) the production of 1O2, O(2), and ICL by CCT and its photoreactive ingredients. The skin photosensitizing (smarting, edema, and erythema responses) and carcinogenic properties of CCT may also be related to the production of 1O2 and O(2) and the formation of ICL which appear to be responsible for inducing the damage to the DNA and cell membrane.
mesh_terms: D000818:Animals; D003033:Coal Tar / Q000494:pharmacology* / Q000627:therapeutic use; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D003849:Deoxyguanosine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006168:Guinea Pigs; D006801:Humans; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D010778:Photochemotherapy; D010787:Photosensitivity Disorders / Q000139:chemically induced; D012867:Skin / Q000378:metabolism; D012871:Skin Diseases / Q000188:drug therapy*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D005609:Free Radicals; D013481:Superoxides; D003033:Coal Tar; D004247:DNA; D003849:Deoxyguanosine; D010100:Oxygen