Podophyllin, but not the constituents quercetin or kaempferol, induced genotoxicity in vitro and in vivo through ROS production

Abstract

The genotoxic potential of podophyllin (PD) was investigated in this study. PD increased bacterial revertants and abnormal chromosomal structures in a concentration-dependent manner, both with and without metabolic activating enzymes, and increased the incidence of micronuclei in imprinted control region mouse reticulocytes. Results from three studied constituents of PD, such as podophyllotoxin, kampferol, and quercetin, suggested that the mutagenic effect of PD was not due to the presence of podophyllotoxin, kampferol, and quercetin and might be related to other components and the formation of reactive oxygen species. The detailed mutagenic mechanisms need further investigation, and the medicinal use of PD needs to be cautioned against.

Keywords::

• Podophyllin
• Genotoxicity
• Ames test
• Chromosome aberration
• Micronucleus
• Reactive oxygen species

Acknowledgments

The authors would like to express our appreciation to all who helped us with this research. The authors thank Dr. Jaw-Jou Kang of the Institute of Toxicology, College of Medicine, National Taiwan University, and Dr. George Hsiao of the Department and Graduate Institute of Pharmacology, College of Medicine, Taipei Medical University, who kindly gave us comprehensive suggestions on the experiments. The authors also thank the Bureau of Food and Drug Analysis, Department of Health, Executive Yuan (Taipei, Taiwan) for supporting this work.