DNA repair, DNA synthesis and cell cycle delay in human lymphoblastoid cells differentially sensitive to the cytotoxic effects of nitrogen mustard.
AffiliationPaterson Laboratories, CHristie Hospital and Holt Radium Institute, Manchester, M20 9BX, United Kingdom
MetadataShow full item record
AbstractTwo cloned human lymphoblastoid cell lines, Raji and TK6, differ in their sensitivity to the cytotoxic effects of nitrogen mustard (HN2). Raji cells exhibit a biphasic response with an initial D value of 0.06 microgram/ml and a final slope of 0.25 microgram/ml. TK6 cells were considerably more sensitive, D0 value 0.02 microgram/ml. Dose-response relationships for delay in cell cycle progression were measured using flow cytometry. Delay in S-phase traverse was concentration-dependent in both cell lines, and at a given concentration was 2-fold greater in TK6 than in Raji. Numbers of crosslinks (determined by alkaline elution) increased linearly with increasing HN2 concentration and were approximately 2-fold higher in TK6 than in Raji. At equal levels of DNA crosslinks, rates of removal were similar in both cell lines. Inhibition of [3H]TdR uptake was concentration-dependent and the extent of inhibition was similar in both cell lines. Recovery from HN2-induced inhibition of cell cycle progression markedly preceded recovery from inhibition of [3H]TdR incorporation suggesting that nucleotide pools are markedly perturbed in HN2-treated cells. The difference in sensitivity of these two cell lines cannot be adequately explained by differences in amounts of initial DNA damage, rates of repair, differential S-phase delay or rate of loss of DNA crosslinks.
CitationDNA repair, DNA synthesis and cell cycle delay in human lymphoblastoid cells differentially sensitive to the cytotoxic effects of nitrogen mustard., 132 (1-2):63-72 Mutat Res
- Investigation of the cell cycle response of normal and Fanconi's anaemia fibroblasts to nitrogen mustard using flow cytometry.
- Authors: Dean SW, Fox M
- Issue date: 1983 Nov
- Relationship between DNA cross-links, cell cycle, and apoptosis in Burkitt's lymphoma cell lines differing in sensitivity to nitrogen mustard.
- Authors: O'Connor PM, Wassermann K, Sarang M, Magrath I, Bohr VA, Kohn KW
- Issue date: 1991 Dec 15
- The role of suppression of DNA synthesis and inhibition of cell cycle progression in cellular sensitivity to alkylation damage.
- Authors: Graham A, Fox M
- Issue date: 1983
- Elevated topoisomerase II activity and altered chromatin in nitrogen mustard-resistant human cells.
- Authors: Tan KB, Mattern MR, Boyce RA, Hertzberg RP, Schein PS
- Issue date: 1987