The Chinese hamster V79 cell mutant V-H4 is phenotypically like Fanconi anemia cells |
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Authors: | M. Z. Zdzienicka F. Arwert I. Neuteboom M. Rooimans J. W. I. M. Simons |
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Affiliation: | (1) MGC, Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Sylvius Laboratory, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands;(2) J.A. Cohen Institute, Interuniversity Research Institute for Radiopathology and Radiation Protection, Leiden;(3) Department of Anthropogenetics, Free University, Amsterdam, The Netherlands |
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Abstract: | It has been shown by genetic complementation analysis that a mitomycin C-sensitive mutant (V-H4) of Chinese hamster V79 cells is the first rodent equivalent of Fanconi anemia (FA) group A. The V-H4 mutant shows many typical characteristics of cells derived from FA patients. V-H4 cells exhibit increased sensitivity towards cross-linking agents as MMC (30-fold), cis-DDP (10-fold), DEB (10-fold), and PUVA (1.6-fold), but an only slightly increased sensitivity to monofunctional alkylating agents (EMS and MMS) and actinomycin D. V-H4 cells are also moderately sensitive to adriamycin (1.6-fold), and not sensitive to H2O2. The levels of chromosomal aberrations induced by MMC and cis-DDP treatment are higher (4- to 6-fold) in V-H4 cells than in the wild-type V79 cells. Genetic complementation analysis with other Chinese hamster mutants hypersensitive to MMC (irs1, irs1SF, UV20 and UV41) indicates clearly that V-H4 belongs to a different, new complementation group. This unique mutant is very stable and can serve as a vehicle to isolate the complementing FA-A gene from normal human DNA. |
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