Environmental and Molecular Mutagenesis (EMM) Editor’s Choice - July 2011
The Editor's Choice for July is “The Human Carcinogen Aristolochic Acid I Is Activated to Form DNA Adducts by Human NAD(P)H:quinone Oxidoreductase Without the Contribution of Acetyltransferases or Sulfotransferases” by Marie Stiborová, Jaroslav Mareš, Eva Frei, Volker M. Arlt, Václav Martínek, and Heinz H. Schmeiser.
Dietary exposure to aristolochic acids is a current public health concern in several parts of the world because these plant-derived substances have been established as potent urothelial tract carcinogens. Stiborová et al. examined the ability of different enzymes to convert aristolochic acid I (AAI) to molecular species capable of generating the DNA adducts ultimately responsible for AA-induced carcinogenesis. They used in silico modeling of three dimensional crystal structures to study potential interactions between NAD(P)H:quinone oxidoreductase (NQO1) and AAI. They used human recombinant NQO1 in vitro to measure NQO1-mediated AAI-DNA adduct formation and the effects of different cofactors. In addition, they investigated the potential activation of AAI by Phase II enzymes and concluded that sulfotransferases and N,O-acetyltransferases do not have major roles in AAI-induced DNA adduct formation. Thus, the work by Stiborová et al. provides a new level of understanding regarding the molecular mechanisms underlying the activation of AAI, an important human carcinogen. Environ. Mol. Mutagen. 52:448-459 (2011) Published 2011 Wiley-Liss, Inc.