Adducts as Biomarkers of Effect of DNA-Reactive Carcinogens

To the Editor:

In their study of macromolecular binding sites of N-acetyl-2-aminofluorene (AAF) in cultured rat hepatocytes, Koch et al. (2018) report findings that “raise the possibility that carcinogenic DNA adducts derived from AAF metabolites form below concentrations of AAF that inhibit replicative and repair DNA synthesis”.

Likewise, in studies of AAF dose-effects in rat liver, Williams et al. (1998, 2015) report formation of DNA adducts at dosages much lower than those required to produce cytotoxicity and enhance DNA synthesis. In fact, adducts are emerging as potentially the most sensitive biomarkers of effect of DNA-reactive carcinogens (Kobets and Williams, 2016).

SUPPLEMENTARY DATA

Supplementary data are available at Toxicological Sciences online.