In:
International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 21 ( 2022-10-28), p. 13125-
Kurzfassung:
Benzo[a]pyrene (B[a] P) is metabolized in the liver into highly reactive mutagenic and genotoxic metabolites, which induce carcinogenesis. The mutagenic factors, including B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) and reactive oxygen species, generated during B[a] P metabolism can cause DNA damage, such as BPDE-DNA adducts, 8-oxo-dG, and double-strand breaks (DSBs). In this study, we mechanistically investigated the effects of quercetin and its major metabolite isorhamnetin on the repair of B[a]P-induced DNA DSBs. Whole−transcriptome analysis showed that quercetin and isorhamnetin each modulate the expression levels of genes involved in DNA repair, especially those in homologous recombination. RAD51 was identified as a key gene whose expression level was decreased in B[a] P−treated cells and increased by quercetin or isorhamnetin treatment. Furthermore, the number of γH2AX foci induced by B[a]P was significantly decreased by quercetin or isorhamnetin, whereas RAD51 mRNA and protein levels were increased. Additionally, among the five microRNAs (miRs) known to downregulate RAD51, miR−34a level was significantly downregulated by quercetin or isorhamnetin. The protective effect of quercetin or isorhamnetin was lower in cells transfected with a miR−34a mimic than in non−transfected cells, and the B[a] P-induced DNA DSBs remained unrepaired. Our results show that quercetin and isorhamnetin each upregulates RAD51 by downregulating miR−34a and thereby suppresses B[a]P-induced DNA damage.
Materialart:
Online-Ressource
ISSN:
1422-0067
DOI:
10.3390/ijms232113125
Sprache:
Englisch
Verlag:
MDPI AG
Publikationsdatum:
2022
ZDB Id:
2019364-6
SSG:
12
