| Abstract
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Previous results from in vivo and in vitro studies show Selenium (Se) may act as an anticarcinogenic agent provides the impetus for exploring the cytotoxic effects of different forms of Se. The BrdU-differential staining technique was used in analyzing the effects of this substance on asynchronously dividing cells, namely, purified lymphocytes from normal human individuals. Three parameters were employed to assess cellular damage. (1) Cell survival at the end of 96 hr. culture period; (2) Changes in the proportion of cells in first, second, and third or subsequent metaphases, M, M2 and M3 respectively; (3) Changes in SCE rate. To establish a baseline SCE frequency the effect of BrdU on three parameters was investigated. BrdU results agreed with previous reports that the analogue perturbs cell cycle kinetics and that SCE are spontaneous events at a rate of 3.84 SCE/cell/2 cell cycles. The genotoxic effects of Se were dependent on the form used, its concentration, and length of exposure to that form. These results support earlier findings indicating the biphasic effect of this substance on cellular growth, i.e. low concentrations stimulate cell proliferation, high levels are anti-proliferative. In addition, our data indicated a differential effect of Se. Based on efficacy on cell survival and suppression of cell division, the following order of toxicity can be stated: Selenodiglutathione > Sodium Selenite > Selenomethionine. In contrast, Selenodiglutathion was the least efficacious compound in SCE induction followed by Selenomethionine and Selenite. Thus, the data of Se, unlike those of BrdU, show no consistent relationship between the examined responses. Considering the strong antitumorigenic properties of Se and the correlation between SCE and carcinogenicity, the effect of Se on pretreatment with N-methyl-N-nitrosourea (MNU), was studied. MNU alone stimulated cell division and resulted in severe reduction of cell survival; however, it was not efficient in SCE induction. It appears from the combined treatment experiments that MNU and Se produce non-additive effects, suggesting a kind of molecular interaction between the two substances. In conclusion, the present data indicates Se by itself is cytotoxic; should Se be used in chemotherapy, keeping in mind the possibility of complicating effects on normal tissues. Obviously, further work is necessary to evaluate the potential chemo-preventive action of Se. Our study represents a step in this direction.
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