S-9 metabolic activation enhances aflatoxin-mediated transformation of C3H/10T1/2 cells

The use of a rat liver S-9 metabolic activation system to enhance aflatoxin B1-mediated transformation of C3H/10T1/2 cells was studied. Under conditions of metabolic activation, the cytotoxicity of Aflatoxin B1 (AFB) was increased approximately 10-fold over that observed in the absence of activation. Similarly, activation increased the transformation of these cells treated with 1 microgram/ml AFB1 greater than 10-fold when cells were treated in the absence of activation with 1 microgram/ml AFB1 for 3 hr, and four-to-fivefold over the transformation observed when cells were treated for 48 hr with 1 microgram/ml AFB1. This same activation procedure also induced the transformation of these cells treated with 10 and 20 micrograms/ml cyclophosphamide in the absence of activation. The use of S-9 metabolic activation greatly increased the sensitivity of AFB1-mediated transformation of C3H/10T1/2 cells, and should expand the range of chemical carcinogens, requiring metabolic activation, in particular mycotoxins related to AFB1, that can be effectively detected and studied in the C3H/10T1/2 cell transformation assay.