Tumor selenium inhibition

In five of six nondietary tumor-promotion experiments, sodium selenide significantly reduced the number of mice with tumors induced by 7,12-dimethyl-benzanthracene (DMBA)-croton oil (1). In these experiments, sodium selenide was applied concomitantly along with croton oil to female Swiss albino mice initiated with DMBA. Riley has also observed a reduction in DMBA-phorbol ester carcinogenesis by sodium selenide (2). The effect of selenium-deficient and selenium-adequate diets on DMBA-croton oil and benzopyrene skin carcinogenesis has also been studied. Supplemental dietary selenium inhibited both types of carcinogenesis. 

Epidemiological studies in humans do not suggest an association between excess exposure to selenium and cancer." Low levels of intake, however, have been associated with an increased risk of developing many kinds of cancers. With the exception of selenium sulfide, most animal studies have shown that selenium compounds inhibit tumorigenesis." High doses of selenium sulfide administered by gavage caused liver tumors in rats and lung... 

Furthermore, while the effect of selenium on the action of direct acting carcinogens is less than observed with compounds requiring metabolic activation, a reduction in total tumor number is often observed. Therefore, selenium probably inhibits both the initiation and promotion phases of carcinogenesis. 

More recent data indicate the efficacy of selenium in inhibiting virally induced tumors can be markedly influenced by the type of diet fed. While selenium addition to the drinking water inhibited tumor formation in mice fed the Oregon State University chow, it had little effect on mice fed Wayne Lab Blocs (56) ... 

The mechanism by which selenium retards virally induced tumorigenesis is unknown. Selenium may inhibit tumor formation by interfering with the replication or transforming action of viruses. Selenium may simply be reducing the proliferation of the transformed cells such that the presence of tumors is not detectable. 

Considerable evidence has shown that selenium can inhibit the growth of experimentally transplanted tumors (65-74) One of the principal cell lines that has been used for many of these studies has been the Ehrlich ascites tumor cell (65-68) Abdullaev et al., (65) showed that the parenteral administration of sodium selenite at a dose of 1 ug per g body weight of the host retarded the growth of this tumor cell line. Additional studies also revealed that similar quantities of jelenium inhibited the growth of Guerin carcinoma, sarcomatous M neoplasms and L-1210 leukemic cells (65, 74) ... 

An enhanced effect of tumor inhibition was observed when selenium was given in combination with X-ray (65) or chemotherapy (74) ... 

Selenium, at 5 X10 M, stimulated the growth of primary cell cultures of normal mammary cells and C4 preneoplastic cells and the established cell line YN-4 but not the growth of D2 preneoplastic cells and tumors in primary cell cultures and of established cell lines CL-S1 and Waz-2t. The differential response of cells from preneoplastic outgrowth lines C4 and D2 and of D2 primary tumors in vitro correlated with the sensitivity of these same cell populations to selenium mediated inhibition of growth and tumorigenesis in vivo. Selenium had little effect on 3 or 4 preneoplastic mammary outgrowth lines. Recent studies by Poirier et al., (70) have shown that... 

Selenium is generally reduced during cellular metabolism (76) Therefore, selenate would yield selenite, followed by a further reduction to selenide (77, 79) Greeder and Milner (67) and Milner and Hsu (74) have reported little difference exists in the efficacy of sodium selenite, sodium selenate and selenium dioxide to inhibit tumor proliferation. 

Schrauzer G, White D, Schneider C. 1976. Inhibition of the genesis of spontaneous mammary tumors in C3H mice Effects of selenium and of selenium-antagonistic elements and their possible role in human breast cancer. Bioinorg Chem 6 265-270. 

Dietary selenium can inhibit chemically as well as virally induced tumors in experimental animals (Shamberger 1970, Schrauzer etal. 1974, 1976, 1980, Griffin 1979,... 

The hallmark of promotion is the increased tumor yield and decreased latency period. If one better understands the mecha-nism(s) of the promotional process, one might be able to intervene in the process and either reverse the process of tumor development or prolong the latency such that tumors would not appear in the normal life span. Experimental data indicate that reversal or inhibition of promotion is possible by administering vitamins A, C or E and the trace metals selenium and zinc. Drugs like the glucocorticoids, protease inhibitors and cyclic MP analogs also inhibit tumor promotion. At present, the exact mechanism of action of these compounds is unknown and many anti-promoters may yet be discovered. 

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