Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-5-30
pubmed:abstractText
The present study was aimed at verifying the occurrence, if any, of in vivo oxidative DNA damage in FA homozygotes, their parents and siblings. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured, by HPLC/EC, in DNA from circulating blood leucocytes from FA homozygotes and their relatives and compared with a group of paediatric and adult healthy subjects. The population studied consisted of: (i) 15 FA homozygotes; (ii) 24 FA heterozygotes; (iii) 11 siblings. The 8-OHdG level in FA homozygotes was significantly higher with respect to age-matched controls, with a mean level of 33.3 +/- 6.8 (mean +/- SE) and 3.9 +/- 0.26 8-OHdG/10(5) dG respectively. The FA parents (heterozygotes) also displayed higher 8-OHdG levels relative to controls. The release of hydroxyl (.OH) and .OH-like radicals from leucocytes was determined by luminol-dependent chemiluminescence (LDCL) in a subgroup of FA homo- and heterozygotes, showing a very large in vivo formation of non-superoxide radicals. Chromosomal instability was also measured in the FA population. When relating either 8-OHdG or LDCL levels to spontaneous or diepoxybutane-induced chromosomal instability (S-CI and DEB-CI respectively), a significant correlation was observed between the 8-OHdG, LDCL and S-CI data. Within families a positive association was found between 8-OHdG levels in homozygotes and their related heterozygotes, suggesting segregation of the genetic defect(s) underlying the abnormal oxidative metabolism. The present study provides evidence for an in vivo pro-oxidant state in FA, in terms of excess formation of .OH and .OH-like radicals, and of DNA hydroxyl adducts. This finding appears to be shared by homozygotes and, to a lesser extent, by heterozygotes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
735-41
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:7728950-Adolescent, pubmed-meshheading:7728950-Adult, pubmed-meshheading:7728950-Aged, pubmed-meshheading:7728950-Aged, 80 and over, pubmed-meshheading:7728950-Child, pubmed-meshheading:7728950-Child, Preschool, pubmed-meshheading:7728950-Chromatography, High Pressure Liquid, pubmed-meshheading:7728950-Chromosomes, Human, pubmed-meshheading:7728950-DNA, pubmed-meshheading:7728950-DNA Damage, pubmed-meshheading:7728950-Deoxyguanosine, pubmed-meshheading:7728950-Epoxy Compounds, pubmed-meshheading:7728950-Fanconi Anemia, pubmed-meshheading:7728950-Female, pubmed-meshheading:7728950-Heterozygote, pubmed-meshheading:7728950-Homozygote, pubmed-meshheading:7728950-Humans, pubmed-meshheading:7728950-Leukocytes, pubmed-meshheading:7728950-Luminescent Measurements, pubmed-meshheading:7728950-Luminol, pubmed-meshheading:7728950-Male, pubmed-meshheading:7728950-Middle Aged, pubmed-meshheading:7728950-Oxidation-Reduction, pubmed-meshheading:7728950-Reactive Oxygen Species, pubmed-meshheading:7728950-Respiratory Burst
pubmed:year
1995
pubmed:articleTitle
In vivo accumulation of 8-hydroxy-2'-deoxyguanosine in DNA correlates with release of reactive oxygen species in Fanconi's anaemia families.
pubmed:affiliation
IST, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't