AF 2 (2-(2-furyl)-3-(5-nitro-furyl)acrylamide) was toxic to Chinese hamster V 79 cells and normal human fibroblasts in aerobic media. However, the toxicity of the
drug was increased many times by
hypoxia. Similarly, the frequency of AF 2-induced
azaguanine- and
ouabain-resistant mutants of V 79 cells was much higher in
hypoxia than under aerobic conditions. Both hamster V 79 cells and human fibroblasts metabolized
AF 2 and other
nitrofurans rapidly only under hypoxic conditions. Human fibroblasts were more sensitive to
AF 2 both under aerobic conditions and in
hypoxia than were V 79 cells under similar conditions. The Chinese hamster cells consistently gave survival curves with marked shoulders while human cells did not. Aerobic cultures of fibroblasts derived from
xeroderma pigmentosum (XP) patients were markedly sensitive to
AF 2 while fibroblasts from two
ataxia telangeictasia patients had normal sensitivity. Under hypoxic conditions the sensitivity of both types of cells was increased but the XP line remained 5--10-fold more sensitive than normal or
ataxia cells. These results suggest that the DNA lesions produced by
AF 2 may be regarded as similar to those produced by ultraviolet light, at least in terms of their repairability in human cells.