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.
Povey
A C
AC
National Cancer Institute, Bethesda, MD.
Plummer
S M
SM
Grafstrom
R C
RC
Harris
C C
CC
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D011090:Polyenes / Q000378:metabolism / Q000633:toxicity*
D005609:Free Radicals; D009153:Mutagens; D011090:Polyenes; C037357:1-(1-glycero)dodeca-1,3,5,7,9-pentaene; D004247:DNA; D005978:Glutathione