Conversion of amoscanate to a mutagenic metabolite in gnotobiotic mice implanted with Streptococcus equinus.

Recent in vitro studies indicate that intestinal bacteria convert amoscanate (4-nitro-4'-isothiocyanodiphenylamine), an antischistosomal drug, to a potent mutagen. The present study indicates that the implantation of germfree mice with Streptococcus equinus, isolated from the small intestine of conventional mice, restores the mutagenic activation of amoscanate in vivo.

An evaluation of the host-mediated assay and body fluid analysis. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The methodologies and status of the Host-Mediated Assay were reviewed using the published literature available up to June 1980. The Working Group reviewed 274 documents, including abstracts, research articles, review articles, and publicly available contracts and grant final reports. From this group, abstracts and reviews were rejected from critical evaluation.

Mutagenicity, tumorigenicity, and electrophilic reactivity of the stereoisomeric platinum(II) complexes of 1,2-diaminocyclohexane.

Without external activation, cis- and trans-dichlorodiammineplatinum(II) (DDP) and the cis, trans(-), and trans(+) forms of dichloro-1,2-diaminocyclohexaneplatinum(II) (DDCP) and sulfato-1,2-diaminocyclohexaneplatinum(II) (SHP) showed a 400-fold range of mutagenicity for Salmonella typhimurium TA100 and TA98; they were 2 to 10 times more mutagenic for strain TA100 than for strain TA98. With strain TA100, trans-DDP was less than 0.5% as mutagenic as the cis isomer, which produced 180 revertants/nmol.

Protection by antibiotics against experimental focal cholangitis produced in mice by a schistosomicidal isothiocyanate.

Oral administration to mice of high doses of 4-isothiocyano-4'nitrodiphenylamine (amoscanate), a potent antischistosomal drug, produced focal necrotizing lesions of the large intrahepatic and extrahepatic bile ducts and the gallbladder. Coadministration of erythromycin and, to a somewhat lesser degree, of paromomycin, markedly reduced the effects of amoscanate on the biliary tract. These results suggest that amoscanate may be converted to a cholangiotoxic product by one or several constituents of the enteric bacterial flora.

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.