Vitamin K1 increases sister chromatid exchange in vitro in human leukocytes and in vivo in fetal sheep cells: a possible role for "vitamin K deficiency" in the fetus.
The levels of the vitamin K-dependent clotting factors are markedly lower in the human fetus and newborn than in older infants and adults. Direct measurement of vitamin K1 in cord plasma records low or undetectable levels. This phenomenon, although the norm, is referred to as vitamin K deficiency and is a significant risk factor for hemorrhage in the fetus and newborn. Sister chromatid exchange (SCE), which may be used as an index of mutagenic activity, was assayed in cultured leukocytes of placental and adult blood following phytohemagglutinin stimulation. The mean number of SCEs per metaphase in human placental blood was 3.32 +/- SE 0.219 as compared with levels of 5.13 +/- SE 0.273 in young adults (p less than 0.01), and in the presence of added vitamin K1 at a concentration of 1 X 10(-6) M the SCE increased significantly in both adult and placental cells. In vitro SCE dose response curves to K1 in the blood of fetal and maternal sheep were obtained. When five fetal sheep were given 1 mg of K1 by catheter into the femoral vein the SCE increased from 3.94 +/- SE 0.15 preinjection to 5.38 +/- SE 0.23 at 24 h postinjection (p less than 0.01). In the pretreatment fetal sheep, serum vitamin K1 was below detectable levels in all seven animals in which it was assayed and reached levels as high as 0.3 X 10(-6) M 1 h post-K1 injection. The low level of K1 in the fetus may in fact confer some biological advantage by reducing the risk of mutagenic events during a period of rapid cell proliferation.
Department of Medicine, University of Manitoba, Manitoba Institute of Cell Biology, Winnipeg, Canada.
L G
LG
Israels
E
E
Friesen
A H
AH
Jansen
E D
ED
Israels
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000187:drug effects*; D012756:Sheep; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D010837:Vitamin K 1 / Q000097:blood / Q000494:pharmacology*; D014813:Vitamin K Deficiency / Q000097:blood / Q000235:genetics*
D010837:Vitamin K 1