Effect of aflatoxin B1 on growth of normal and malignant rat fibroblasts in tissue culture (DNA synthesis).

The effect of aflatoxin B1 on rat embryo fibroblasts WREF, the transformed line of rat fibroblasts AWRF-1 derived from WREF and the XC line of rat fibroblasts transformed by Rous sarcoma virus has been compared. By determining growth inhibition of cultured cells and inhibition of colony formation WREF have been shown to have the sensitivity to AFB1 about 33 times greater than XC cells and 7 times greater than AWRF-1 cells. In accordance with these results, it has been found that the inhibition of DNA synthesis and the binding of 3H-AFB1 to the TCA-insoluble cell fraction proceeds much more rapidly in WREF than in XC and AWRF-1 cells. These results suggest that WREF cells are capable of a more rapid metabolic activation of AFB1 to toxic metabolite AFB1-8, 9-oxide, probably owing to higher levels of cytochrome P-450-dependent microsomal oxidases. The resistance of cells to AFB1 fairly correlates with the ability of cells to grow in semisolid agar medium and the culture time.