The possible role of free radical reactions in carcinogenesis

H. B. Demopoulos, D. D. Pietronigro, E. S. Flamm, M. L. Seligman

Research output: Contribution to journalReview articlepeer-review

82 Scopus citations


Free radical reactions in carcinogenesis may be important at several points in this multi-step process. However, their most relevant aspect may be to help explain the role of disordered nutrition. Laboratory animal research and world-wide human epidemiology studies have demonstrated that excessive consumption of fats greatly increases the risk of developing several common forms of cancer. It is well known that 'fat-loading' with polyunsaturates, or peroxidized lipids is an effective method for inducing a wide variety of pathologic free radical reactions because usually there is not a concomitant, balanced increase in antioxidant consumption. Molecular oxygen is a free radical gas, and this property, coupled with its preferential solubility in fats poses a constant free radical stress and a continuing production of lipid oxidation products. Our normal, endogenous antioxidants can protect us against this daily, ongoing free radical pathology. Excess fat ingestion and obesity not only 'dilute' the endogenous antioxidant systems, but also include the likelihood that lipid hydroperoxides have been consumed in repetitive quantities; these are thought to enhance the metabolic activation of other carcinogens, and to act as carcinogens themselves, e.g., certain of the cholesterol hydroperoxides. Prudent diets that reduce fat consumption should help to decrease the risk of developing certain cancers such as colo-rectal, and breast, which constitute the predominant cancer burden in the United States. The promotion stages of carcinogenesis seem to be the most modulatable aspects, and involve the integrity of membranes and perhaps membrane lipids. A diet that greatly reduces fat intake will automatically lead to relative increases in the concentrations of available, endogenous, normally occurring antioxidants; this would, in turn, create the most favorable cellular circumstances to combat the free radical reactions in promotion. The development of antioxidants as a supplement to those which occur naturally in fresh fruits and vegetables would appear to be an unnecessary exercise, except: (1) for those circumstances where fresh fruits and vegetables are either unavailable, or are not regularly consumed, (2) where processed foods contain lipids that must be protected, as with the beneficial addition of BHT, and (3) where exposure to carcinogenic factors has been so high, that some supplementation with safe antioxidants is indicated, e.g., exposure to ionizing radiation.

Original languageEnglish (US)
Pages (from-to)273-303
Number of pages31
JournalJournal of Environmental Pathology and Toxicology
Issue number4
StatePublished - Dec 1 1980
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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