Cell cycle defect in connection with oxygen and iron sensitivity in Fanconi anemia lymphoblastoid cells

Experimental Cell Research
M PootH Hoehn

Abstract

Fanconi anemia (FA) is an autosomal recessive disorder involving progressive pancytopenia, skeletal malformations, and a predisposition to leukemia. The in vitro growth of FA fibroblasts is impaired, due to a defective G2 phase traverse of the cell cycle. Analyzing the cell cycle of lymphoid cell lines (LCLs) obtained from peripheral blood of FA patients by transformation with Epstein-Barr virus, we found a similar G2 phase defect, which was dependent upon the oxygen concentration. In addition, FA cells exhibited hypersensitivity toward cis-dichlorodiammineplatinum and mitomycin C, and moderate sensitivity toward trans-dichlorodiammineplatinum. FA cells, however, showed no elevated sensitivity toward paraquat, an intracellular generator of superoxide radicals, or cumene hydroperoxide, a model organic peroxide. Chelating iron with low concentrations of o-phenanthrolin improved cell proliferation and G2 phase transit of FA cells at 20% oxygen, but little at 5% oxygen. LCL cultures from healthy subjects were inhibited in their proliferation rate at all concentrations of o-phenanthrolin. Exposure to excess iron, on the other hand, was very toxic to FA cells at 20%, but less toxic at 5% oxygen. In conclusion, the FA mutation leads t...Continue Reading

Citations

Nov 25, 1998·British Journal of Haematology·A A ClarkeT R Rutherford
Feb 1, 1997·Human Molecular Genetics·W LiebetrauH Hoehn
Nov 10, 2001·Annual Review of Genomics and Human Genetics·R E Moses
Dec 13, 2003·Biological Chemistry·Maria KontouManfred Schweiger
May 26, 2009·Mutation Research·Kornelia NevelingDetlev Schindler
Jul 8, 2005·European Journal of Haematology·Giovanni PaganoAdriana Zatterale
May 27, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Giovanni Pagano, Hagop Youssoufian
Mar 4, 2015·Pediatric Blood & Cancer·Giovanni PaganoFederico V Pallardó
Jul 14, 1998·Somatic Cell and Molecular Genetics·P JohnstoneR E Moses
Jun 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sara Bravo-NavasCarlos Pipaón
May 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M PootP S Rabinovitch

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