Flavonoids and DNA Repair in Prostate Cancer
Annual rept., 1 Dec 2003-30 Nov 2004
CALIFORNIA UNIV LOS ANGELES
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Oxidative DNA damage has been closely linked to cancer development. An active DNA repair system is critical to prevent the occurrence of mutations leading to carcinogenesis. It was the objective of this investigation to test the hypothesis that natural products such as flavonoids are able to stimulate the repair of oxidative DNA damage. For this purpose LNCaP prostate tumor cells were exposed to FeSO4 to induce oxidative DNA damage 8-hydroxydeoxyguanosine determined by HPLC. DNA repair was evaluated by following the decrease of oxidative DNA damage over time. We were able to demonstrate that in LNCaP cells exposed to naringenin 80 micromoles per liter oxidative DNA repair activity was increased by 24 compared to media treated control. RT PCR results demonstrated that the increase in DNA repair was associated with an increased mRNA expression of three BER repair enzymes important in the repair of oxidative DNA damage 8-oxoguanin-DNA glycosylase 1 hOGG1, apurinicapyrimidinic endonuclease APE and DNA polymerase beta DNA pol-beta . We observed the maximum stimulatory effect on mRNA expression at 24 hours of naringenin treatment. Currently additional flavonoids -- and in the near future flavonoid metabolites and breakdown products -- will be tested for their DNA repair-stimulatory activity.
- Medicine and Medical Research