An Integrated Mode of Action for Dietary Antioxidant and Lipid-Modulated UV-Radiation Carcinogenesis

摘要

A hypothesis for the role of free radicals in mutation, ageing and cancer was elaborated by Harman in 1962, who suggested that it might be possible to reduce the rate of production of damage by free radicals through at least three dietary changes: (ⅰ) caloric reduction, i.e. lowering the level of free radical reactions arising in the course of normal metabolism; (ⅱ) supplement the diet with one or more free radical reaction inhibitors; and (ⅲ) minimise dietary components such as polyunsaturated fats that tend to increase the level of free radical reactions. The rationale for these recommendations rested upon the supposition that "if free-radical reactions contribute to the degradation of biological systems, and if the level of deleterious reactions can be lowered significantly by diet, then such dietary alterations should have a beneficial effect" . Much earlier, Roffo had recognised the importance of lipids in tumour development and had suggested that cholesterol was a "heliotropic" substance, migrating and accumulating in anatomical sites routinely exposed to UV rays from the sun and subsequently degraded to a substance of carcinogenic activity. This presented an attractive theory as cholesterol is naturally occurring and widely distributed in biological tissues. A flurry of investigative activity continued throughout the 1950s in search of carcinogenic cholesterol derivatives. It was just such a study that led Baumann and Rusch to observe that a fat-enhanced diet shortened the tumour latent period in animals receiving chronic UV irradiation.