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CAROTENOID PIGMENTS AND PROTECTION AGAINST PHOTOSENSITIZATION: HOW STUDIES IN BACTERIA SUGGESTED A TREATMENT FOR A HUMAN DISEASE MICHEUNE M. MATHEWS-ROTH* Most of us can enjoy exposure to the sun without much discomfort unless we expose ourselves to its rays for an unduly long time. A small group of people cannot tolerate exposure to the sun even for a few minutes because they develop distressing reactions in their skin [I]. Although most ofthese people are unusually sensitive to the range oflight that causes sunburn (290—320 nanometers), clinical studies over the past several decades have shown that some of these people are sensitive to visible light (>400 nanometers). The phenomenon of sensitivity to visible light seems such an unlikely event that it poses important fundamental and applied questions to biology and medicine. At the turn of this century, Oscar Rabb, in Germany, and subsequently many other workers, observed that certain bacteria and protozoa could be killed by visible light in the presence of porphyrins, chlorophyll, or other pigments; these photosensitizing substances occurred naturally within the cells of certain organisms or could be added to suspensions of organisms which did not normally contain photosensitizers . Later, certain patients who were sensitive to visible light were found to have porphyrins in their tissues in unusuaUy high levels, and the suggestion was made that these porphyrins were causing the patients ' unusual sensitivity to light. In some of these patients, the accumulation of porphyrins was found to be on a genetic basis, and in others, the porphyria was acquired [I]. The most common form oflightsensitive porphyria is erythropoietic protoorphyria (EPP), definitively described only about 20 years ago by Magnus [2] and Langhof [3]. ?Channing Laboratory, Department of Medicine, Harvard Medical School, 180 Longwood Avenue, and Brigham and Women's Hospital, Boston, Massachusetts 02115.© 1984 by The University of Chicago. AU rights reserved. 003 1-5982/85/2801-0415$01 .00 Perspectives in Biology and Medicine, 28, 1 ¦ Autumn 1984 \ 127 Patients with EPP usually complain of itching, burning, redness, and swelling of the exposed skin, sometimes after exposure to as little as 2 or 3 minutes ofsunlight [I]. Occasionally after prolonged exposure to light, the skin may break out into crusted, weeping lesions that heal with some degree ofscarring. Many patients have such severe discomfort after only brief exposures to light that they have had to organize their lives and careers so as to avoid going outdoors during the brightest sunlight hours. Most patients with EPP are forced to wear protective clothing— trousers, long sleeves, hats, and often gloves—whenever they go out in daylight, and so it is not surprising that many adults with EPP prefer night work. The disease is especially difficult for children; children with EPP cannot play outdoors in the usual manner. Until recendy there had been no effective treatment for the photosensitivity associated with this disease, other than avoiding exposure to sunlight . Topical sunscreens, effective for the prevention of ordinary sunburn , give no significant protection in EPP. However, studies in bacteria showed that carotenoid pigments functioned to protect the organisms against photosensitization, and these studies suggested a possible approach to the treatment ofphotosensitivity. How this idea was developed into a workable and rather effective treatment for EPP is the subject of this article. In 1955, Drs. William Sistrom, Roger Stanier, and their colleagues found that the carotenoid pigments of photosynthetic bacteria could protect the bacteria against lethal photosensitization by their own chlorophyll [4]. This observation came about as a result of experiments with the photosynthetic bacterium Rhodopseudomonas sphéroïdes. Photosynthetic bacteria, like green plants, contain chlorophyll and carotenoids , although the structure of chlorophyll and some of the chemical reactions in photosynthesis are different in bacteria than in higher plants. The mutant studied by Sistrom and co-workers, which they called the "blue-green" mutant, did not produce colored carotenoids but accumulated colorless precursor pigments in the cell. They found that when the blue-green mutant was grown in the presence oflight and air, growth stopped, chlorophyll was destroyed, and the cells were killed. However, the wild type, with its carotenoid pigments, was not injured by growth in light and air. Futher studies by these workers demonstrated that it was...


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