Enhanced sensitivity of lymphoblastoid cells from individuals carrying the mutation for the fragile X syndrome to the clastogenic effects of FUdR.
Individuals known to carry the mutation for the fragile X syndrome can sometimes be identified cytogenetically by the presence of a fragile site on the X chromosome at q27.3. The frequency of cells bearing this fragile site is known to be enhanced by culturing the cells in folic acid deficient medium and/or by introducing folic acid metabolism inhibitors such as FUdR. In this study FUdR induction of chromosomal aberrations other than the fragile X was investigated. Lymphoblastoid cells from an obligate carrier, a mentally retarded male and a control were cultured in folic acid deficient medium in the presence of FUdR and harvested at various times after culture initiation. The frequency of chromosome and chromatid breaks was found to be higher in cells from the individuals carrying the mutation for the fragile X syndrome. The frequency of micronuclei, an indirect index of chromosome breakage, was also more elevated in cells from these individuals than in cells from the control. These findings are of potential importance to carrier detection of this common genetic disorder.
D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D002875:Chromosomes / Q000187:drug effects; D005260:Female; D005467:Floxuridine / Q000494:pharmacology*; D005492:Folic Acid / Q000502:physiology; D005600:Fragile X Syndrome / Q000378:metabolism*; D006580:Genetic Carrier Screening; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D012729:Sex Chromosome Aberrations / Q000378:metabolism*
D005467:Floxuridine; D005492:Folic Acid