Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1994-11-3
pubmed:abstractText
The genetic and epigenetic effects of nutritional folate deficiency were studied in two Chinese hamster ovary (CHO) cell lines. The CHO-AA8 cell line (hemizygous at the aprt locus) and CHO-UV5 (DNA repair-deficient mutant of AA8) were cultured in Ham's F-12 medium or in custom-prepared Ham's F-12 medium lacking folic acid, thymidine, and hypoxanthine. Cells cultured acutely in the folate deficient medium exhibited initial growth arrest, followed by massive cell death and DNA fragmentation into nucleosomal multimers characteristic of apoptosis. Although prolonged culture in the folate deficient medium was cytostatic and lethal to the majority cells, minor subpopulations in both cell lines failed to initiate cell death, exhibited phenotypic abnormalities, and adapted a selective growth advantage under marginal folate conditions. These "resistant" clones exhibited major alterations in deoxynucleotide pools associated with an increase in mutant frequency at the aprt locus as detected by resistance to cytotoxicity in 8-azaadenosine. The mutation frequency in the DNA repair-deficient CHO-UV5 cells was approximately 100-fold greater than that in the parental AA8 clones, underscoring the importance of DNA repair under conditions of folate deficiency and nucleotide pool imbalance. The enhanced mutation frequency in the DNA repair-competent folate-deficient CHO-AA8 cells suggests that DNA repair activity is less effective under folate-deficient conditions. These results add to the accumulating clinical and experimental evidence relating chronic folate deficiency to genomic instability and carcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5075-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
In vitro folate deficiency induces deoxynucleotide pool imbalance, apoptosis, and mutagenesis in Chinese hamster ovary cells.
pubmed:affiliation
Division of Nutritional Toxicology, Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas 72079.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't