Genotoxic mechanisms of fecapentaene-12 in human cells

Fecapentaenes are mutagenic to both bacterial and human cells and can morphologically transform murine Balb/c 3T3 cells. DNA damage induced by fecapentaene-12 includes DNA cross-links, DNA protein cross-links and single strand breaks. Oxy- and alkyl-radicals have been detected in aqueous solution using spin traps coupled with EPR. Oxy-radicals thus formed can then directly damage DNA to form DNA SSB's or 80HdG. Radiolabeling studies suggest that fecapentaene-12 may also form specific adducts either directly or after aldehyde formation. Hence fecapentaene-12 may cause DNA damage by two distinct mechanisms i.e., directly (alkylation) or indirectly (via free radicals). Reactions of fecapentaene-12 with GSH tend to support this hypothesis. Possible synergistic interactive effects of DNA damage caused by direct and indirect mechanisms are currently under investigation.