|Observations on vitamin K deficiency in the fetus and newborn: has nature made a mistake?|
|PMID: 8747698 Owner: NLM Status: MEDLINE|
|The microsomal mixed function oxidase system metabolizes xenobiotics (Phase I) to products that, if not activated and conjugated for excretion (Phase II), are capable of forming conjugates with cellular macromolecules, including DNA, resulting in toxic, mutagenic, or carcinogenic events. Benzo(a)pyrene (BP), a polycyclic aromatic hydrocarbon, is a model carcinogen for this system. Vitamin K1 (phylloquinone) is a regulator of BP metabolism. These studies demonstrate that K1 is capable of increasing Phase I metabolism and decreasing glutathione transferase activity (Phase II) in chick embryo liver; that deprivation of K1 reduces BP/DNA adducts in mouse liver and reduces tumor formation in mice given intraperitoneal BP; and that K1 supplementation increases BP induced tumor formation in mice. However, epidemiologic studies indicate that children of mothers who smoke during pregnancy may not be at increased risk of cancer. It is known that the placentas from these pregnancies exhibit markedly increased levels of arylhydrocarbon hydroxylase induced by the polycyclic aromatic hydrocarbons in tobacco smoke, but there is no corresponding increase in this enzyme activity in the fetus in such pregnancies. We suggest that the low vitamin K level is a secondary protective mechanism for xenobiotics, such as BP, that may escape the primary placental screen. The recently described role of vitamin K-dependent Gla protein as ligands for receptor tyrosine kinases, also establishes K as a link in cell growth and transformation. It is proposed that the small total body pool of K1 in the adult, which is sufficient only to meet continuing needs, and the even smaller pool in the fetus are protective. This protective effect of low K1 levels is particularly important in the presence of the high mitotic rates and rapid cell turnover in the avian embryo and mammalian fetus.|
|L G Israels; E D Israels|
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|Type: Journal Article; Review|
|Title: Seminars in thrombosis and hemostasis Volume: 21 ISSN: 0094-6176 ISO Abbreviation: Semin. Thromb. Hemost. Publication Date: 1995|
|Created Date: 1996-10-24 Completed Date: 1996-10-24 Revised Date: 2006-03-07|
Medline Journal Info:
|Nlm Unique ID: 0431155 Medline TA: Semin Thromb Hemost Country: UNITED STATES|
|Languages: eng Pagination: 357-63 Citation Subset: IM|
|Department of Medicine, University of Manitoba, Manitoba Institute of Cell Biology, Winnipeg, Canada.|
|APA/MLA Format Download EndNote Download BibTex|
Carcinogens / pharmacokinetics
DNA Adducts / metabolism
Fetal Diseases / physiopathology*
Fetus / metabolism*
Infant, Newborn / metabolism*
Liver / embryology
Mice, Inbred ICR
Microsomes, Liver / enzymology
Mixed Function Oxygenases / metabolism
Neoplasms / chemically induced, epidemiology
Neoplasms, Experimental / chemically induced
Placenta / enzymology
Prenatal Exposure Delayed Effects*
Smoking / adverse effects
Vitamin K / administration & dosage, adverse effects
Vitamin K 1 / physiology*, toxicity
Vitamin K Deficiency / drug therapy, embryology, physiopathology*
Warfarin / pharmacology
Xenobiotics / pharmacokinetics*, toxicity
|0/Carcinogens; 0/DNA Adducts; 0/Xenobiotics; 0/benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; 12001-79-5/Vitamin K; 55097-80-8/7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; 81-81-2/Warfarin; 84-80-0/Vitamin K 1; EC 1.-/Mixed Function Oxygenases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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