Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis.
The cancer chemopreventive effect of selenium cannot be fully accounted for by the role of selenium as a component of the antioxidant enzyme glutathione peroxidase, which suggests that chemoprevention occurs by another mechanism. Several studies have shown that thiol oxidation and free radical generation occur as a consequence of selenium catalysis and toxicity. In the present study, we evaluated three different selenium compounds; selenite, selenocystamine, and selenomethionine to determine the relative importance of the prooxidative effects of these compounds with regard to their ability to induce apoptosis. The experimental results suggest that, in addition to supporting an increased activity of glutathione peroxidase, an antioxidant function that the three selenium compounds did with equal efficacy, catalytic selenite, and selenocystamine generated 8-hydroxydeoxyguanosine DNA adducts, induced apoptosis and were found to be cytotoxic in mouse keratinocytes. The noncatalytic selenomethionine was not cytotoxic, did not generate 8-hydroxydeoxyguanosine adducts and did not induce cellular apoptosis at any of the selenium concentrations studied. In keratinocytes, apoptosis may be initiated by superoxide (O2*-) and oxidative free radicals that are generated by selenite and selenocystamine, but not by selenomethionine.
Stewart
M S
MS
Department of Pathology, Texas Tech University, Health Sciences Center, Lubbock 79430, USA.
Spallholz
J E
JE
Neldner
K H
KH
Pence
B C
BC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003538:Cystamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D004249:DNA Damage; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D012643:Selenium / Q000494:pharmacology* / Q000633:toxicity*; D012645:Selenomethionine / Q000494:pharmacology / Q000633:toxicity; D018038:Sodium Selenite / Q000494:pharmacology / Q000633:toxicity; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D016566:Organoselenium Compounds; D013481:Superoxides; C014807:selenocystamine; D012645:Selenomethionine; D005979:Glutathione Peroxidase; D005978:Glutathione; D012643:Selenium; D018038:Sodium Selenite; D003538:Cystamine