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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1998-9-16
pubmed:abstractText
We studied the embryonic and maternal genotoxicity of pyrimethamine (PYR), a potent teratogen and folate antagonist, using alkaline single cell gel electrophoresis (SCG, or Comet) assay as modified by us (we used isolated nuclei instead of isolated cells). ICR mice were treated on the 13th day of pregnancy with a single oral dose of 50 mg PYR/kg. Six maternal organs (liver, kidney, lung, brain, spleen, bone marrow), maternal and fetal placentas, and two embryos were taken 6 and 16 h after treatment; the embryos were divided into head and body portions. Each sample was minced, homogenized gently, and centrifuged. The nuclei from the precipitates were used. PYR induced DNA damage in all maternal organs except spleen and bone marrow 6 h after administration. The DNA damage in all the affected organs was less at 16 h than at 6 h, and that of the kidney and brain returned to control level at 16 h. PYR also induced DNA damage in maternal and fetal placentas and embryos that was detected at 6 and 16 h, with greater damage at 6 h. Co-treatment of folinic acid calcium salt (FNA, 10 mg/kg ip), a reduced active folate form, prevented the PYR-induced DNA damage in all target tissues examined 6 h after treatment. These data indicate that the observed embryonic and maternal DNA damage caused by PYR may be related to folate deficiency, and that the modified alkaline SCG assay can be used to predict fetal/embryonic genotoxicity in vivo, in addition to the organ-specific maternal genotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
415
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
69-77
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Detection of pyrimethamine-induced DNA damage in mouse embryo and maternal organs by the modified alkaline single cell gel electrophoresis assay.
pubmed:affiliation
Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Japan. s.tsuda@iwate-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't