Treatment of Human HeLa Cells with Black Raspberry Extracts Enhances the Removal of DNA Lesions by the Nucleotide Excision Repair Mechanism

Abstract

As demonstrated by us earlier and by other researchers, a diet containing freeze-dried black raspberries (BRB) inhibits DNA damage and carcinogenesis in animal models. We tested the hypothesis that the inhibition of DNA damage by BRB is due, in part, to the enhancement of DNA repair capacity evaluated in the human HeLa cell extract system, an established in vitro system for the assessment of cellular DNA repair activity. The pre-treatment of intact HeLa cells with BRB extracts (BRBE) enhances the nucleotide excision repair (NER) of a bulky deoxyguanosine adduct derived from the polycyclic aromatic carcinogen benzo[a]pyrene (BP-dG) by ~24%. The NER activity of an oxidatively-derived non-bulky DNA lesion, guanidinohydantoin (Gh), is also enhanced by ~24%, while its base excision repair activity is enhanced by only ~6%. Western Blot experiments indicate that the expression of selected, NER factors is also increased by BRBE treatment by ~73% (XPA), ~55% (XPB), while its effects on XPD was modest (<14%). These results demonstrate that BRBE significantly enhances the NER yields of a bulky and a non-bulky DNA lesion, and that this effect is correlated with an enhancement of expression of the critically important NER factor XPA and the helicase XPB, but not the helicase XPD.

Oxidative DNA Damage and Repair: Mechanisms, Mutations, and Relation to Diseases

“…It has been known for a while that the diet containing black raspberries (BRB) reduces the level of DNA damage and carcinogenesis in cell cultures and animal models [ 10 , 11 ]. Sales et al [ 12 ] have demonstrated that the inhibition of oxidatively induced DNA damage in human HeLa cells treated with black raspberry extracts (BRBE) is associated with a significant growth of the nucleotide excision repair (NER) yields of a bulky deoxyguanosine adduct derived from the polycyclic aromatic carcinogen benzo[a]pyrene (BP-dG) and a non-bulky DNA lesion, guanidinohydantoin (Gh). These effects are correlated with an increase in the expression of the critically important NER factor XPA and the helicase XPB, but not the helicase XPD.…”