Investigation of the cell cycle response of normal and Fanconi's anaemia fibroblasts to nitrogen mustard using flow cytometry.
dc.contributor.author | Dean, S W | |
dc.contributor.author | Fox, Margaret | |
dc.date.accessioned | 2015-01-02T16:28:00Z | |
dc.date.available | 2015-01-02T16:28:00Z | |
dc.date.issued | 1983-11 | |
dc.identifier.citation | Investigation of the cell cycle response of normal and Fanconi's anaemia fibroblasts to nitrogen mustard using flow cytometry. 1983, 64:265-79 J Cell Sci | en |
dc.identifier.issn | 0021-9533 | |
dc.identifier.pmid | 6662859 | |
dc.identifier.uri | http://hdl.handle.net/10541/337764 | |
dc.description.abstract | Cell survival has been measured in normal and Fanconi's anaemia (FA) human fibroblasts after treatment with the bifunctional alkylating agent, nitrogen mustard (HN2). Two FA cell lines exhibited 6- to 10-fold greater sensitivity than the normal cell line. Flow cytometry was used to investigate the effects of HN2 on cell cycle progression of normal and FA cells. After 0.1 microgram/ml HN2 (surviving fraction, s.f. = 0.8) normal cells exhibited an S phase accumulation within 6 h, followed by a transient G2 delay. At higher doses of HN2, the S phase delay became more pronounced and there was considerably greater accumulation of cells in G2. HN2 at 0.01 microgram/ml (s.f. = 0.8) induced no detectable S or G2 delay in FA cells. A higher dose, 0.1 microgram/ml (s.f. = 0.13 and 0.29), again induced no S phase delay, but a gradual accumulation of cells in G2 was observed up to 78 h after treatment. The presence of an S phase delay in normal cells after HN2 treatment may be important in allowing time for DNA repair before completion of DNA synthesis. The absence of such a delay in FA cells suggests that an inability to delay S phase traverse in response to DNA damage from bifunctional alkylating agents may contribute to the sensitivity of FA cells to such drugs. | |
dc.language.iso | en | en |
dc.rights | Archived with thanks to Journal of cell science | en |
dc.subject.mesh | Anemia, Aplastic | |
dc.subject.mesh | Cell Cycle | |
dc.subject.mesh | Cell Survival | |
dc.subject.mesh | Cells, Cultured | |
dc.subject.mesh | DNA | |
dc.subject.mesh | Dose-Response Relationship, Drug | |
dc.subject.mesh | Fanconi Anemia | |
dc.subject.mesh | Fibroblasts | |
dc.subject.mesh | Flow Cytometry | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mechlorethamine | |
dc.title | Investigation of the cell cycle response of normal and Fanconi's anaemia fibroblasts to nitrogen mustard using flow cytometry. | en |
dc.type | Article | en |
dc.contributor.department | Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester M20 9BX | en |
dc.identifier.journal | Journal of Cell Science | en |
html.description.abstract | Cell survival has been measured in normal and Fanconi's anaemia (FA) human fibroblasts after treatment with the bifunctional alkylating agent, nitrogen mustard (HN2). Two FA cell lines exhibited 6- to 10-fold greater sensitivity than the normal cell line. Flow cytometry was used to investigate the effects of HN2 on cell cycle progression of normal and FA cells. After 0.1 microgram/ml HN2 (surviving fraction, s.f. = 0.8) normal cells exhibited an S phase accumulation within 6 h, followed by a transient G2 delay. At higher doses of HN2, the S phase delay became more pronounced and there was considerably greater accumulation of cells in G2. HN2 at 0.01 microgram/ml (s.f. = 0.8) induced no detectable S or G2 delay in FA cells. A higher dose, 0.1 microgram/ml (s.f. = 0.13 and 0.29), again induced no S phase delay, but a gradual accumulation of cells in G2 was observed up to 78 h after treatment. The presence of an S phase delay in normal cells after HN2 treatment may be important in allowing time for DNA repair before completion of DNA synthesis. The absence of such a delay in FA cells suggests that an inability to delay S phase traverse in response to DNA damage from bifunctional alkylating agents may contribute to the sensitivity of FA cells to such drugs. |