Deactivation of furyl furamide (AF-2) by rat-liver microsomes and its implication in short-term tests for...

The genetic activity of AF-2 in both bacteria and yeast rapidly disappeared in the presence of rat-liver microsomal fraction (S9 mix). Incubation of AF-2 with S9 mix even for 10 min at 37 degrees C was sufficient to inactivate it completely. Data available in the literature suggest that activation of AF-2 is necessary for its geno-toxic effect. The activation step may involve reduction of the nitrofuran to an amino group probably by the enzyme reductase I. Most cultured cell systems, such as bacteria, yeast, Neurospora, mammalian cells and human lymphocytes, can probably bring about this reduction. However, the rapid disappearance of the genetic activity of AF-2 in the presence of rat-liver homogenate suggests that rat-liver microsomes may further metabolize the reduction products to inactive forms. Thus, it becomes necessary to test even those chemicals that are mutagenic per se, with mammalian microsomal preparations before their mutagenic/carcinogenic potentialities can be assessed in short-term tests.