title: Cytogenetic response to G2-phase X irradiation in relation to DNA repair and radiosensitivity in a cancer-prone family with Li-Fraumeni syndrome.
abstract: Noncancerous skin fibroblasts from six family members with Li-Fraumeni syndrome, five with cancer of diverse tissue origin and one with a premalignant neoplasm, showed a high frequency of chromatid aberrations, 94 to 119 breaks and 58 to 95 gaps per 100 metaphase cells arrested with colcemid 0.5 to 1.5 h after X irradiation (1.75 x 10(-2) C/kg). This response results from deficient repair of the radiation-induced DNA damage. In contrast, skin fibroblasts from two unrelated normal controls and a spouse showed 19 breaks and 17 to 19 gaps per 100 cells. Whereas all six members of the cancer-prone family had a radioresistant phenotype, only four had an inherited p53 mutation. Fibroblasts from a radioresistant family member showed the same extent of chromatid damage directly (0 to 0.5 h) after G2-phase X irradiation as those from the radiosensitive control spouse. We conclude, therefore, that radiosensitivity, as determined by cell killing in asynchronous populations of skin fibroblasts, is unrelated to chromosomal sensitivity to G2-phase X irradiation. However, the persistence of a high frequency of chromatid breaks and gaps at 0.5 to 1.5 h after G2-phase X irradiation, a manifestation of deficient DNA repair, is associated with proneness to cancer in this family.
authors.affiliation: Department of Pathology, College of Medicine, Howard University, Washington, DC 20059.
authors.forename: R
authors.initials: R
authors.lastname: Parshad
authors.forename: F M
authors.initials: FM
authors.lastname: Price
authors.forename: K F
authors.initials: KF
authors.lastname: Pirollo
authors.forename: E H
authors.initials: EH
authors.lastname: Chang
authors.forename: K K
authors.initials: KK
authors.lastname: Sanford
mesh_terms: D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects; D016195:G2 Phase / Q000528:radiation effects*; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D011836:Radiation Tolerance