Host-mediated transformation: metronidazole

Abstract

To evaluate the possible genotoxic effects of the drug, metronidazole in the fetus, we employed the hamster embryo host-mediated assay. Pregnant golden Syrian hamsters were fed metronidazole at doses ranging from 200 mg/kg to 900 mg/kg on days 11 and 12 of pregnancy. Embryonic cells obtained from the treated animals were studied in vitro for morphologic evidence of transformation. To further assess the significance of the in vitro finding, cells from mass culture were tested for their ability to grow in soft agar. The drug-treated cells and cells previously treated with diethyl nitrosamine (positive controls) showed comparable growth characteristics. To confirm the neoplastic potential of the drug-treated embryonic cells, subcultivated cells from the tenth passage were implanted into nude mice and irradiated immunosuppressed hamsters. Cells from the 300 mg/kg treatment produced fibrosarcoma in nude mice but not in the irradiated hamsters. Cells from no other dose level employed in the study produced tumors in host animals. It is concluded that metronidazole is capable of vertical transmission of potential genotoxic effects to the fetus.