title: Role of DNA repair in malignant neoplastic transformation of human mammary epithelial cells in culture.
abstract: Epithelial cells derived from normal human mammary tissue were examined for capacity to repair radiation-induced chromatin DNA damage. Repair capacity was estimated by quantifying chromatid aberrations in metaphase cells arrested 0.5-1.5 h after X-irradiation during G2. The parental cells at passage 12 had 19 chromatid breaks and 16 gaps per 100 metaphase cells, representing efficient repair. Of two continuous cell lines, derived after benzo[a]pyrene treatment, A1 maintained the efficient repair phenotype through passage 50, while a subline of A1 developed the repair-deficient phenotype characterized by a 3- to 5-fold higher frequency of chromatid breaks or gaps. This line was transformed to tumorigenic cells by HaMSV and SV40 T antigen. The second continuous line B5 and derivatives had 102-165 chromatid breaks and 87-134 gaps per 100 metaphases (deficient repair phenotype). This line was transformed to tumorigenic cells by KiMSV. As reported previously for human epidermal keratinocytes, acquisition of this repair-deficient phenotype appears to be an early requisite step in the malignant neoplastic transformation of human cells in culture.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
authors.forename: K K
authors.initials: KK
authors.lastname: Sanford
authors.forename: F M
authors.initials: FM
authors.lastname: Price
authors.forename: J S
authors.initials: JS
authors.lastname: Rhim
authors.forename: M R
authors.initials: MR
authors.lastname: Stampfer
authors.forename: R
authors.initials: R
authors.lastname: Parshad
mesh_terms: D000328:Adult; D001940:Breast / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002478:Cells, Cultured; D002843:Chromatin / Q000528:radiation effects; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology / Q000528:radiation effects; D005260:Female; D016195:G2 Phase / Q000528:radiation effects; D006801:Humans; D008677:Metaphase
chemical_list: D002843:Chromatin