Lin, Wei-ShengWei-ShengLinCheng, Wan-ChenWan-ChenChengHo, Pin-YuPin-YuHoHo, Chi-TangChi-TangHoMIN-HSIUNG PAN2023-09-252023-09-252023-08-2300218561https://scholars.lib.ntu.edu.tw/handle/123456789/635760Benzo[a]pyrene (B[a]P) is a genotoxic polycyclic aromatic hydrocarbon that is metabolized by cytochrome P450 family 1 enzymes (CYP 1s) and can bind to DNA to form DNA adducts, leading to DNA damage and increased colorectal cancer risk. Previous studies have shown polymethoxyflavones to have a high potential for anticancer effects by regulating CYP 1s, especially nobiletin (NBT) and 5-demethylnobiletin (5-DMNB). However, the effects of NBT and 5-DMNB on B[a]P metabolism remain unclear. Therefore, this study aimed to clarify the effects of NBT and 5-DMNB on B[a]P-induced DNA damage in vitro and in vivo. In NCM460 cells, 5-DMNB and NBT appeared to reduce the metabolic conversion of B[a]P by regulating the aryl hydrocarbon receptor (AhR)/CYP 1s signaling pathway. This process protected NCM460 cells from B[a]P's cytotoxic effects by decreasing DNA damage and suppressing B[a]P diol-epoxide-DNA adduct formation. In BALB/c mice, 5-DMNB and NBT also protected against B[a]P-induced DNA damage. Altogether, these findings indicate that 5-DMNB and NBT attenuate B[a]P-induced DNA damage by modulating biotransformation, highlighting their chemopreventive potential against B[a]P-induced carcinogenesis. Therefore, 5-DMNB and NBT are promising agents for colorectal cancer chemoprevention in the future.en5-demethylnobiletin; BPDE-DNA adduct; CYP 1s; benzo[a]pyrene; nobiletinjournal article10.1021/acs.jafc.3c03347376107752-s2.0-85169892538https://api.elsevier.com/content/abstract/scopus_id/85169892538