In Vivo Genotoxicity of Ginkgo Biloba Extract in gpt Delta Mice and Constitutive Androstane Receptor Knockout Mice

The National Toxicology Program study of Ginkgo biloba ex-tract (GBE), a herbal supplement, reported concerns regarding genotoxicity and clear evidence of hepatocarcinogenicity and liver hypertrophy in mice. To clarify the genotoxicity of GBE in vivo, we performed reporter gene mutation assay using gpt delta mice. We also used a combined liver comet assay and bone marrow mi-cronucleus assay using C3H-derived constitutive androstane re-ceptor knockout (CARKO) and wild-type mice. No remarkable in-creases in gpt or Spi − mutation frequencies were observed in DNA extracted from the livers of gpt delta mice that had been exposed to GBE up to 2000 mg/kg bw/day. In the comet and micronucleus assays, no statistically significant increases in positive cells were ob-served at doses up to 2000 mg/kg bw/day of GBE in either mouse genotype. The present study provides clear evidence that GBE is not genotoxic in vivo. Our results indicate that GBE-induced hep