Partial complementation of the Fanconi anemia defect upon transfection by heterologous DNA. Phenotypic dissociation of chromosomal and cellular hypersensitivity to DNA cross-linking agents.
Transfectants obtained by mouse DNA-mediated gene transfer in Fanconi anemia (FA) primary fibroblasts from the genetic complementation groups A and B were examined for the frequencies of chromosomal aberrations and cytotoxicity following treatments by cross-linking agents. Cells from group A (FA 150), which is the most sensitive to such agents, are partially corrected for both the chromosomal and cellular hypersensitivity to 8-methoxypsoralen photoaddition. In contrast, after treatment with mitomycin C (MMC), only the chromosomal sensitivity is re-established to a near normal level. The opposite is true for FA group B cells (FA 145), i.e. cell survival to MMC is partially corrected, whereas the frequency of MMC-induced chromosomal aberration remains close to that of the untransfected cells. The partial phenotypic correction of the two end points examined is interpreted as indicating either a gene dosage effect or the necessity of introducing more than one gene type in order to achieve complete recovery of a normal phenotype. The phenotypic dissociation between the clastogenic and cellular hypersensitivity to cross-linking agents may offer the opportunity of isolating separately the responsible gene(s) by conventional rescue techniques.
Diatloff-Zito
C
C
CNRS URA 1292, Institut Curie, Paris, France.
Rosselli
F
F
Heddle
J
J
Moustacchi
E
E
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004247:DNA / Q000235:genetics*; D004351:Drug Resistance; D005199:Fanconi Anemia / Q000235:genetics*; D005816:Genetic Complementation Test; D006801:Humans; D008730:Methoxsalen / Q000494:pharmacology; D051379:Mice; D010641:Phenotype; D014162:Transfection; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D004247:DNA; D008730:Methoxsalen