Chemopreventive agents: selenium.

Prediagnostic serum selenium and risk of cancer.

The authors were asked by the Editors of ACS Chemical Biology to write an article titled “Why Nature Chose Selenium” for the occasion of the upcoming bicentennial of the discovery of selenium by the Swedish chemist Jons Jacob Berzelius in 1817 and styled after the famous work of Frank Westheimer on the biological chemistry of phosphate [Westheimer, F. H. (1987) Why Nature Chose Phosphates, Science 235, 1173–1178]. This work gives a history of the important discoveries of the biological processes that selenium participates in, and a point-by-point comparison of the chemistry of selenium with the atom it replaces in biology, sulfur. This analysis shows that redox chemistry is the largest chemical difference between the two chalcogens. This difference is very large for both one-electron and two-electron redox reactions. Much of this difference is due to the inability of selenium to form π bonds of all types. The outer valence electrons of selenium are also more loosely held than those of sulfur. As a result,...

Why Nature Chose Selenium

In July, 1988, more than 300 scientists from 29 different countries gathered at Tiibingen, W. Germany, in order to spend 4 days discussing their favourite trace element, selenium. This meeting continued the good tradition of three previous meetings held in Corvallis/Oregon, 1976, in Lubbock/Texas, 1980, and in Beijing/China, in 1984. Incidentally, the University of Tiibingen provided a unique historical background for a Symposium devoted to recent advances in biochemistry, pharmacology, human nutrition and human health; here, the first independent depart ment of Physiological Chemistry in Germany was founded in 1845. Pro fessor H9Ppe-Seyler elucidated here the hemin structure and his student Friedrich Miescher discovered the nucleic acids. This book contains one-half of the oral or poster presentations which were selected before the meeting was held on the basis of a one page abstract. It is the reader who will have to decide whether this time consuming policy of quality assessment was warranted or not."

Selenium in biology and medicine

The potential for chemical intervention (chemoprevention) as a means of halting or delaying the process of carcinogenesis is assessed as a strategy for reducing the incidence of human cancer. The process of carcinogenesis is dissected into its constituent steps, thereby exposing sites for intervention. These sites are then critically discussed with regard to the existence of chemicals active at these sites using data gained from the laboratory and from epidemiological studies, intrinsic problems or advantages associated with intervention at specific sites in the carcinogenic process, and practical aspects of intervention in humans. The design and potential long-term positive and negative consequences of chemoprevention clinical trials are critically discussed, with the objective of exposing the major differences that exist between clinical trials in cancer chemoprevention and those in cancer chemotherapy. Results of completed prevention trials and details of ongoing trials are presented and discussed. Based on the laboratory, epidemiological, and clinical evidence presented, it is concluded that chemoprevention offers excellent prospects as a means of reducing cancer incidence. Among currently available agents, the retinoids possess the best combination of properties. However, much more research is needed to optimize drugs and protocols and to develop interim end points for assessing response. The authors finally caution that overambitious claims for the prospects for chemoprevention may lead to reduced emphasis on the need for changes in life-style (principally in smoking and diet) that are viewed as having the greatest potential for reducing cancer incidence.

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Rationale and Strategies for Chemoprevention of Cancer in Humans

(1972). Effect of Dietary Selenium on N-2 Fluorenyl-Acetamide (FAA)-Induced Cancer in Vitamin E Supplemented, Selenium Depleted Rats. Clinical Toxicology: Vol. 5, No. 2, pp. 187-194.

Effect of Dietary Selenium on N-2 Fluorenyl-Acetamide (FAA)-Induced Cancer in Vitamin E Supplemented, Selenium Depleted Rats

(1973). Relationship of Dietary Selenium Concentration; Chemical Cancer Induction; and Tissue Concentration of Selenium in Rats. Clinical Toxicology: Vol. 6, No. 3, pp. 487-495.

Relationship of dietary selenium concentration; chemical cancer induction; and tissue concentration of selenium in rats.

(1972). Selenium Poisoning in Domestic Animals and Its Relationship to Man. Clinical Toxicology: Vol. 5, No. 2, pp. 175-186.

J. R. Harr

Papers

Effect of Dietary Selenium on N-2 Fluorenyl-Acetamide (FAA)-Induced Cancer in Vitamin E Supplemented, Selenium Depleted Rats

Relationship of dietary selenium concentration; chemical cancer induction; and tissue concentration of selenium in rats.

Selenium Poisoning in Domestic Animals and Its Relationship to Man

Selenium deficiency lesions in rats fed vitamin E supplemented rations.