Role of Dietary Fat in Ultraviolet Light–Induced Carcinogenic Expression

Abstract

EditorialThe indictment of fat as a dietary constituent that potentiates carcinogenesis arose from a study of Watson and Mellanby in 1930 [1]. Animal diets containing high levels of butterfat (12.5-25%) were shown to enhance coal tar-induced skin tumor formation. After this seminal observation, intense investigations of the effects of dietary fat on chemically-induced carcinogenesis were conducted during the 1930s through the 1950s. There were several conclusions from these studies that are noteworthy [2]. These, however, must be tempered by the fact that many of these early studies failed to control for major dietary parameters, e.g., caloric density. And although much of the exacerbation of fat on tumor formation reported in these early studies could be explained on the basis of increased caloric intake, fat, per se, increased the rate of tumor formation, particularly when total caloric intake was restricted. Also, much of the exacerbation by fat on tumor formation occurred during the post initiation stage of carcinogenesis. Baumann and Rusch [3] first demonstrated that dietary fat also had an influence on ultraviolet light (UVL) induced carcinogenesis. These investigators employed a high-fat diet that contained up to 30% hydrogenated cottonseed oil. This resulted in a four week shorter tumor latent period than that which occurred in low-fat controls. However, this line of investigation ended with the advent of World War II and was not resumed for nearly 45 years. This was unfortunate as UVL-carcinogenesis is the main etiologic agent in skin carcinogenesis. Nearly 90% of all human skin cancers are the result of solar UVL [4]. Thus, studies of skin carcinogenesis employing UVL are the most relevant to the clinical condition. There are other advantages to employing a physical carcinogenic agent over chemical carcinogens in dietary studies. UVL involves no activation/detoxification of the presumed carcinogenic species; no competitive chemical inhibition; no binding to target molecules; and no transport to respective target sites. Changing the cells chemical milieu through dietary modification could have an impact on any of these activities affecting chemical carcinogenesis. UVL allows investigation of the direct underlying mechanisms of dietary modification of the skin cancerization process.Dietary lipid was further implicated in cancer when Denham Harmon [5] developed the Free Radical Theory of disease. Cognizant of the vulnerability of polyunsaturated fatty acids to free radical attack, he recommended that dietary levels of PUFA be reduced in order to reduce cancer risk [6]. Indeed, the first report on diet and UVL carcinogenesis following the seminal observation in 1939, appeared to be in agreement with Harman's recommendation. Mice were fed semidefined, isocaloric diets containing 0.75 to 4.0 % (w/w) omega-6 fatty acid (Corn oil), and subjected to a UVL regimen. The tumor latent period was dramatically lengthened and tumor multiplicity reduced as the dietary PUFA level was reduced [7].These tumor parameters ...