苯并(a)芘(B[a]P)是一种致基因突变的多环芳烃，通过细胞色素P450家族1酶(CYP 1s)代谢，可以与DNA结合形成DNA加合物，导致DNA损伤并增加结直肠癌的风险。以前的研究表明，多甲氧基黄酮通过调节CYP 1s，尤其是柚皮甙(NBT)和5-去甲基柚皮甙(5-DMNB)，具有较高的抗癌效果潜力。然而，NBT和5-DMNB对B[a]P代谢的影响尚不清楚。因此，本研究旨在阐明NBT和5-DMNB对B[a]P诱导的体外和体内DNA损伤的影响。在NCM460细胞中，5-DMNB和NBT通过调节芳香烃受体(AhR)/CYP 1s信号通路，似乎减少了B[a]P的代谢转化。这一过程通过减少DNA损伤和抑制B[a]P二氧化环氧-DNA加合物的形成，保护了NCM460细胞免受B[a]P的细胞毒性作用。在BALB/c小鼠中，5-DMNB和NBT也保护免受B[a]P诱导的DNA损伤。总的来说，这些发现表明，5-DMNB和NBT通过调节生物转化减轻了B[a]P诱导的DNA损伤，突显了它们对B[a]P诱导的癌变的化学预防潜力。因此，5-DMNB和NBT是未来结直肠癌化学预防的有希望的药物。

Benzo[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.