Relationship of DNA strand breakage produced by bromodeoxyuridine to topoisomerase II activity in Bloom-syndrome fibroblasts.
Cells from patients with Bloom syndrome, a cancer-prone disorder with cutaneous photosensitivity and spontaneous chromosome breakage, exhibit an abnormally increased number of sister-chromatid exchanges following treatment with 5-bromodeoxyuridine (BrdU). This effect has been postulated to be mediated by abnormal topoisomerase II activity. We used alkaline elution to measure DNA single-strand breakage following prolonged exposure to BrdU. Five-day exposure to BrdU produced equal numbers of alkali-labile sites in normal and Bloom-syndrome fibroblasts. These breaks were not protein-associated but were produced by alkali. Treatment with topoisomerase II inhibitors induced similar frequencies of DNA single-strand breaks in normal and Bloom-syndrome fibroblasts. These findings imply that BrdU incorporation into cellular DNA induces alkali-labile DNA lesions that are independent of topoisomerase II activity in Bloom and normal cells.
Pommier
Y
Y
Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Rünger
T M
TM
Kerrigan
D
D
Kraemer
K H
KH
D001816:Bloom Syndrome / Q000235:genetics*; D001973:Bromodeoxyuridine / Q000009:adverse effects; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects* / Q000528:radiation effects; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000201:enzymology; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D014965:X-Rays / Q000009:adverse effects
D004247:DNA; D004250:DNA Topoisomerases, Type II; D001973:Bromodeoxyuridine