Sister-chromatid exchange induction by sodium selenite: plasma protein-bound selenium is not the active SCE-inducing metabolite of Na2SeO3.
Sodium selenite (Na2SeO3) is an anticarcinogenic/antimutagenic/anticlastogenic agent that under certain incubation conditions induces sister-chromatid exchanges (SCEs), unscheduled DNA synthesis, and chromosome aberrations. Previous work has shown that SCE induction by Na2SeO3 depends on the presence of red blood cells (RBCs). Therefore, Na2SeO3 uptake and release by RBCs was studied in the present report as was the effect of plasma protein-bound selenium, the end product of Na2SeO3 metabolism by RBCs, on the SCE frequency of purified lymphocyte cultures. Na2SeO3 uptake by human whole blood, RBCs in plasma, RBCs in fetal calf serum, and RBCs in Hanks' balanced salt solution occurs rapidly, reaching a maximum after 2 min (37 degrees C). Release of Na2SeO3 from RBCs depends on the presence of plasma proteins to which the metabolized selenium becomes bound. In spite of the fact that plasma protein-bound selenium is the major product of Na2SeO3 metabolism by RBCs, the SCE frequency of purified lymphocyte cultures was unchanged when plasma protein-bound selenium (7.90 X 10(-6) and 1.19 X 10(-5) M) was added to the medium for the final 19 h of incubation. Further study showed that Na2SeO3 could induce SCEs in blood cultures that had been washed to remove plasma proteins and incubated in medium 199, a maintenance medium lacking fetal calf serum. These findings indicate that a Na2SeO3 metabolite other than plasma protein-bound selenium is responsible for Na2SeO3's SCE-inducing ability in human whole-blood cultures.
D002478:Cells, Cultured; D002850:Chromatography, Gel; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D009153:Mutagens; D020887:Selenious Acid; D012643:Selenium / Q000378:metabolism* / Q000494:pharmacology; D012854:Sister Chromatid Exchange
D009153:Mutagens; D020887:Selenious Acid; D012643:Selenium