Linked Life Data

1176851

Source:http://linkedlifedata.com/resource/pubmed/id/1176851

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1975-12-30
pubmed:abstractText
The glutamine analogue, 6-diazo-5-oxo-L-norleucine (DON), has been shown to inhibit biosynthesis of purines and glycosaminoglycans, presumably by blocking the glutamine-dependent steps in the biosynthetic pathways. The teratogenic potential of DON on the developing mouse limb-bud in vivo and in vitro was studies in an attempt to discriminate whether DON is exerting its teratogenic effect by interfering with glycosaminoglycan or purine metabolism. A single intramuscular injection of DON (0-5 mg/kg) to ICR/DUB mice on day 10 of gestation resulted in 76% resorption, while fetuses surviving to day 17 exhibited growth retardation, median cleft lip, and limb malformation. Concurrent administration of L-glutamine (250 mg/kg) provided no protection against resorption of malformations, while 5-aminoimidazolecarboxamide (AIC, 250 mg/kg) decreased the resorption rate to 34% without significantly altering the incidence of malformations. Injection of DON alone on day 11 resulted in 87% of fetuses exhibiting limb formations, with only 2% resorption. Concurrent injection of AIC decreased the frequency of limb malformations to 32% L-Glutamine, D-glucosamine, or inosinic acid were without any protective effect in vivo. DON (5mug/ml medium) added in vitro to organ cultures of day 11 mouse limb-buds caused all limbs to evidence cartilage abnormalities. In this system, either L-glutamine ro D-glucosamine (0-5 mg/ml medium) provided protection against DON effects while AIC (0-5 mg/ml medium) offered no protection in vitro. These data suggest that DON exerts its effects in vivo by interfering with purine metabolism while in vitro its teratogenic action may be interruption of glycosaminoglycan biosynthesis. This may reflect upon the relative importance of growth and differentiation to limb development in vivo and in vitro. These data infer that limb development in vitro relies more on the differentiative process (differentiation of cartilage) than on growth, whereas limb development in vivo is dependent, at this stage, to a greater extent on growth for normal phenotypic expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-0752
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
355-70
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1975
pubmed:articleTitle
Limb development in mouse embryos: protection against teratogenic effects of 6-diazo-5-ox-L-norleucine (DON) in vivo and in vitro.
pubmed:publicationType
Journal Article