Document Detail


Flow cytometric characterization of the response of Fanconi's anemia cells to mitomycin C treatment.
MedLine Citation:
PMID:  6804195     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNA flow histogram analysis, using 33342 Hoechst as a stain, has been used to detect the effect of the potentially bifunctional alkylating agent, mitomycin C (MMC) on dermal fibroblasts from patients with Fanconi's anemia (FA), a hereditary human disease characterized by pancytopenia, hypersensitivity to DNA-crosslinking agents, congenital abnormalities and a predisposition for neoplasia. At 24 or 48 hr after a 2-hr exposure to 0.05 or 0.10 micrograms/ml MMC, (3)HdT incorporation was reduced to a greater extent in FA cells than in normal cells. Cells sorted from the last half of S phase showed a slightly greater inhibition of (3)HdT incorporation than did those sorted from the first half of S. Fanconi's anemia cells exhibited a marked accumulation in the G(2) + M peak of flow histograms following exposure to MMC. Twenty-four hr after treatment with .0.5 micrograms/ml MMC, the G(2) + M fraction of FA cells (eight lines) increased to more than 0.5 from a control value of approximately 0.02. Both normals (six lines) and heterozygotes (eight lines) showed, on the average, much less of a G(2) + M increment than did FA cells, even after exposure to 0.1 micrograms/ml MMC. Examination of cells sorted from the G(2) + M peak revealed that MMC-treated FA cells were blocked prior to mitosis. To determine whether the response of FA cells was specific for bifunctional alkylating agent, cells were also treated with ethylmethanesulfonate, a monofunctional agent. Twenty-four hours after exposure to 0.25 or 0.5 mg/ml ethylmethanesulfonate, FA and normal cells showed similar, small increases in the G(2) + M peak. The results suggest the utility of flow cytometry in the diagnostic evaluation of fibroblasts from patients suspected of having Fanconi's anemia.
Authors:
T N Kaiser; A Lojewski; C Dougherty; L Juergens; E Sahar; S A Latt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cytometry     Volume:  2     ISSN:  0196-4763     ISO Abbreviation:  Cytometry     Publication Date:  1982 Mar 
Date Detail:
Created Date:  1982-07-19     Completed Date:  1982-07-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8102328     Medline TA:  Cytometry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  291-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alkylating Agents / pharmacology
Anemia, Aplastic / genetics*
Cell Cycle
DNA Repair*
DNA Replication / drug effects
Fanconi Anemia / genetics*
Flow Cytometry
Heterozygote
Humans
Mitomycin
Mitomycins / pharmacology*
Mitosis / drug effects
Grant Support
ID/Acronym/Agency:
GM21121/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Alkylating Agents; 0/Mitomycins; 50-07-7/Mitomycin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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