Mutagenic activation of an antischistosomal drug by enteric Streptococcus sps in vitro and in vivo.

Previous studies have shown that a new antischistosomal drug, 4-isothiocyano-4'-nitro diphenylamine (CGP 4540, amoscanate), is not mutagenic in vitro, but the urines of animals treated with this drug have mutagenic activity. Mutagenicity can be eliminated by coadministration of some antibacterial agents and is not demonstrable in germ-free animals. The present study describes attempts to isolate and identify intestinal microorganisms responsible for the mutagenic activation of amoscanate. Streptococcus equinus, isolated from the intestinal tract of mice, as well as some other species of Streptococcus, were found to produce mutagenic activation of amoscanate when introduced into animals pretreated with antibacterial agents. Similarly, incubation of these strains with amoscanate in vitro resulted in the formation of a mutagenic product.