Noncovalent DNA binding and the mechanism of oxidative DNA damage by fecapentaene-12.

The fecapentaenes are a group of mutagenic, polyunsaturated lipids that are produced endogenously in the human gastrointestinal tract. Previous studies show that the fecapentaenes cause oxidative DNA damage, but the chemical mechanisms by which this occurs remain unclear. The data presented here indicate that fecapentaene-12 causes direct oxidative DNA damage via production of the reactive oxygen species O2*-, H2O2, and HO*. In addition, evidence is presented indicating that fecapentaene-12 associates noncovalently with duplex DNA. Fecapentaene-12 provides an interesting new example highlighting the potential for hydrophobic long chain hydrocarbons to associate noncovalently with duplex DNA.