title: Induction of fragile sites by fluorodeoxyuridine and caffeine accompanies with misincorpolation of endogenous uridine nucleotide into DNA of feline fibroblasts.
abstract: Fluorodeoxyuridine, an inhibitor of thymidylate synthetase, is known to induce chromosomal fragile sites. The drug treatment may cause deprivation of intracellular thymidine nucleotide pool followed by a serious imbalance of deoxynucleotide pool. Though the stress is probably related to the induction of folate-sensitive fragile sites, the exact mechanism is still to be investigated. The present study has been carried out to test the possibility that the fragile sites are originated, at least in part, from incorpolated uracil residues. The incorpolated uracil residue can be detected by a novel assay for abasic sites after treatment with uracil-DNA N-glycosylase (UDG). About 2.7 abasic sites per 10(4) nucleotides were detected in the DNA extracted from feline fibroblasts after the treatment with FUdR and caffeine. By digesting the DNA with UDG prior to the assay, significant increase in the number of abasic sites were observed. These results indicate that the large amount of uracil residues are present in the feline fibroblast DNA under the condition which induces chromosomal fragile sites.
authors.affiliation: Laboratory of Veterinary Radiology, Osaka Prefecture University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: A
authors.initials: A
authors.lastname: Shiomi
authors.forename: A
authors.initials: A
authors.lastname: Asaeda
authors.forename: F
authors.initials: F
authors.lastname: Ohashi
authors.forename: S
authors.initials: S
authors.lastname: Matsuyama
authors.forename: H
authors.initials: H
authors.lastname: Ide
authors.forename: Y
authors.initials: Y
authors.lastname: Takamori
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002415:Cats / Q000235:genetics*; D002478:Cells, Cultured; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D004247:DNA / Q000378:metabolism*; D045647:DNA Glycosylases; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005467:Floxuridine / Q000494:pharmacology*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D014498:Uracil / Q000378:metabolism; D014500:Uracil Nucleotides / Q000378:metabolism*; D051981:Uracil-DNA Glycosidase
chemical_list: D014500:Uracil Nucleotides; D005467:Floxuridine; D002110:Caffeine; D014498:Uracil; D004247:DNA; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase