title: Investigation of the cell cycle response of normal and Fanconi's anaemia fibroblasts to nitrogen mustard using flow cytometry.
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.
mesh_terms: D000741:Anemia, Aplastic / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005199:Fanconi Anemia / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008466:Mechlorethamine / Q000494:pharmacology*
chemical_list: D008466:Mechlorethamine; D004247:DNA