An experimental basis for carcinogenic effects of ultraviolet radiation

Mathematics – Logic

Scientific paper

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Scientific paper

Several hypotheses to explain ultraviolet carcinogenesis have been advanced. One such theory contended that cholesterol was directly involved in actinic carcinogenesis. Although the hypothesis, in its original form, was generally abandoned by the scientific community, it has been revived and modified from time to time as structures and functions of steroid hormones become more clearly understood. In essence it suggests that carcinogenic substances, structurally related to steroid hormones might result from photochemical conversion of cholesterol. Although some compounds with such properties have been isolated under controlled chemical conditions, until recently the failure to find such compounds in biological systems had cast serious doubt upon the validity of this hypothesis. It has now been demonstrated that cholesterol-derived oxidation products are formed in human skin upon exposure to ultraviolet light. One of the products formed is known to possess carcinogenic properties when administered to experimental animals. Furthermore, it has been reported by other investigators that the control mechanism for cholesterol synthesis is absent in liver tumors. Whether this biochemical lesion plays a causal role in the etiology of this disease is unknown but altered cholesterol metabolism has also been implicated in actinically induced skin cancer. It has been demonstrated in this laboratory that skin sterol synthesis is inhibited by light. The principal site of action of light on sterol synthesis appears to be prior to the formation of acetyl coenzyme A in the biosynthetic pathway. Sterol-derived photoproducts produce similar effects as light upon sterol synthesis. These observations suggest more than just a coincidental role of light upon sterols and sterol metabolism in the etiology of skin cancer.

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