Aldehyde sensitivity of human FA cells and the detoxification of aldehydes by aminoguanidine. (A) Formaldehyde dose-dependent survival of EUFA316 human FA-G mutant lymphoblastoid cells compared with an isogenic, FANCG-complemented EUFA316 control. Complementation of patient cells was performed by stably transducing FANCG-mutant EUFA316 cells with a retrovirus expressing a wild-type human FANCG complementary DNA. EUFA316 and EUFA316+FANCG cells were cultivated in RPMI 1640 medium supplemented with 10% fetal bovine serum and penicillin/streptomycin. (B) Aminoguanidine shows dose-dependent rescue of EUFA316 cells from formaldehyde-induced cell death. (C) MMC dose-dependent survival of EUFA316 and wild-type controls. (D) Aminoguanidine provided a mild protection on EUFA316 cells from MMC-induced cell death. (E-F) Statistical quantitation of radials and chromosomal breaks in 259i human FA-A fibroblasts treated with C3, the ADH5 inhibitor. Metformin was added to the cell culture at 10 µM and maintained at the same concentration throughout the experiment. One hour later, C3 was added at 100 µM. Forty-eight hours later, cells were harvested for breakage and radial analysis. Data are combined results from 4 independent experiments.