EXPRESSION OF THE FANCONI-ANEMIA GENE FAC IN HUMAN CELL-LINES - LACK OF EFFECT OF OXYGEN-TENSION

Fanconi anemia (FA) is a recessively inherited disease characterized b y bone marrow failure, congenital anomalies, chromosomal instability a nd hypersensitivity to crosslinking agents. Some of the cellular defec ts of FA defect are known to be responsive to the ambient oxygen conce ntration. We examined the responsiveness of the FA complementation gro up C (FAC) gene to changes in oxygen concentration using two types of human cell lines, hypoxia-responsive Hep3B hepatoma cells and Epstein- Barr virus-immortalized lymphoblasts (normal and FA complementation gr oups B and C). Although the expression of erythropoietin in Hep3B cell s was induced in response to the hypoxia-mimicking agent CoCl2, there was no concomitant induction in FAC expression as assessed by mRNA lev els and immunoprecipitable protein, and no detectable change in the cy toplasmic location of the FAC polypeptide as determined by indirect im munofluorescence. In human lymphoblasts we examined the effect of oxyg en (0.1%-95% 0(2)) on cell proliferation and FAC expression. FA lympho blasts had the expected hypersensitivity to the cytostatic effect of h yperoxia, while in both control and FA lymphoblasts FAC mRNA levels we re unaffected by oxygen. Our results indicate that ambient oxygen is n ot a regulator of the FAC gene.