title: Lack of effect of inhibitors of DNA synthesis/repair on the ionizing radiation-induced chromosomal damage in G2 stage of ataxia telangiectasia cells.
abstract: The relationship between the repair processes occuring at the G2 phase of the cell cycle and cytogenetic damage in ataxia telangiectasia (AT) cells was studied. Lymphoblastoid cells derived from normal, heterozygote AT (HzAT) and three AT patients were exposed to X-rays or fission neutrons and post-treated with inhibitors of DNA synthesis/repair, such as inhibitors of DNA polymerases alpha, delta and epsilon (cytosine arabinoside, ara-C; aphidicolin, APC; buthylphenylen-guanine, BuPdG) or ribonucleotide reductase (hydroxyurea, HU). A strong increase of radiation-induced chromosomal aberrations was observed in normal and HzAT cells post-treated with ara-C, APC and HU, but not in the presence of BuPdG. No enhancing effect was observed in cells derived from AT patients, except for HU post-irradiation treatment. These results suggest that the enzymes that can be inhibited by these agents are not directly involved in the repair of radiation damage induced in G2 cells from AT patients, indicating that probably the AT cells that we used lack the capability to transform the primary DNA lesions into reparable products, or that AT cells might contain a mutated form of DNA polymerase resistant to the inhibitors.
authors.affiliation: Dipartimento di Genetica e Biologia Molecolare, Università La Sapienza, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Antoccia
authors.forename: F
authors.initials: F
authors.lastname: Palitti
authors.forename: T
authors.initials: T
authors.lastname: Raggi
authors.forename: C
authors.initials: C
authors.lastname: Catena
authors.forename: C
authors.initials: C
authors.lastname: Tanzarella
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D002869:Chromosome Aberrations; D004260:DNA Repair / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D016195:G2 Phase; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D004259:DNA-Directed DNA Polymerase; D006918:Hydroxyurea