“…Although for a long time PCBs were thought to be strictly promoting carcinogens, a lower chlorinated congener (PCB3) was shown to induced point mutations in rat livers in vivo (Lehmann et al, 2007), and, in agreement with this, recent evidence suggests that particularly the lower-chlorinated congeners can be oxidized to genotoxic metabolites, such as arene oxides and quinone species (Espandiari et al, 2003, Espandiari et al, 2004, Robertson and Ludewig, 2011). In fact, the quinone metabolites of PCB3 increase gene mutations in vitro at low micromolar concentrations (Zettner et al, 2007), induce strand breaks (Xie et al, 2010), bind to and inhibit the nuclear protein topoisomerase II (Bender et al, 2006, Bender and Osheroff, 2007, Srinivasan et al, 2001, Srinivasan et al, 2002) and reduce telomerase activity resulting in shortened chromosomal telomeres in cells in culture (Jacobus et al, 2008). Interestingly, only the para -dihydroxy metabolite of PCB3 induced polyploidization and only the ortho -dihydroxy metabolite caused sister chromatid exchanges (Flor and Ludewig, 2010) indicating a binding to other, so far unidentified cellular proteins, as mediators of these genotoxic effects.…”