Involvement of topoisomerase II inhibition in clastogenic activity of trans-b-Nitrostyrene

Trans-b-nitrostyrene (b-NS) is used as chain stopper in styrene type polymerization reactions. Interestingly, NS displays promising anti-tumour potential, due to its profound pro-apoptotic properties. We have previously demonstrated that b-NS-triggered formation of DNA strand breaks (SBs), particularly double-strand breaks (DSBs), participates in apoptosis induction. DSB-formation, as determined in the neutral comet-assay, was comparable to that of the topoisomerase II (TopoII) poison etoposide. Therefore, we investigated whether b-NS-induced DNA-damage is also based on inhibition of the breakage-resealing process of TopoII action. b-NS, in contrast to ethyl methane sulfonate (EMS), induced no DNA-damage in an acellular comet-assay, indeed pointing to an enzyme-linked process of DNA-breakage. Furthermore, induction of SBs by b-NS-treatment was strongly related to cell proliferation, as highly proliferating L5178YTK+/- mouse lymphoma cells were signifi