學生姓名:
劉詠潔
指導教授:
黃崇雄
學期:
115上
摘 要:
Benzo[a]pyrene (BaP) is a representative environmental pollutant belonging to the class of polycyclic aromatic hydrocarbons (PAHs). It is mainly generated through the incomplete combustion of organic matter, and humans may be exposed to BaP through contaminated foods and foods prepared by high-temperature cooking methods, such as grilling and frying. PAH exposure is known to increase the risk of allergic and other diseases through immunomodulatory and pro-inflammatory effects. This integrative study investigated the effects of oral BaP exposure on the gut microbiota, immune responses, and gastrointestinal carcinogenic risk. In the first study, female C57BL/6 mice were subjected to combined exposure to BaP and ovalbumin (OVA). BaP was orally administered at 50 μg/mouse/day for 23 consecutive days. Intestinal histopathology, intestinal permeability, Th1/Th2-related cytokines, OVA-specific IgE and IgG1, MCPT-1, and alterations in the gut microbiota were evaluated. The results showed that BaP aggravated OVA-induced intestinal mucosal injury and inflammatory cell infiltration, increased intestinal permeability, and elevated IL-4, IL-5, IL-13, OVA27 specific IgE/IgG1, and MCPT-1 levels, indicating enhanced Th2-type immune responses and mast cell activation. In addition, BaP altered the composition and functional profiles of the gut microbiota. Bacterial strains carrying BaP degradation30 related genes were identified, and some strains reduced BaP-induced cytotoxicity in Caco-2 cells, suggesting a potential bioremediation or detoxification role of the gut microbiota.In the second study, male C57BL/6 mice were orally administered BaP at 3 or 6 μg/kg/day for 60 days to evaluate gastrointestinal toxicity and early carcinogenic risk associated with long-term low-dose exposure. BaP-DNA adduct accumulation was most prominent in the colon and stomach and was accompanied by tissue inflammation and mucosal injury. Serum IL-6 and TNF-α levels were significantly increased, while the expression of NF-κB, IL-6, SOD1, β-catenin, and MUC1 was elevated in the stomach and colon. In contrast, p53 and MUC2 expression decreased at the higher BaP dose, indicating that prolonged BaP exposure may promote chronic inflammation, oxidative stress, DNA damage, and dysregulation of carcinogenesis-related signaling pathways.Overall, oral BaP exposure may induce gut microbiota dysbiosis, intestinal barrier disruption, Th2-type allergic responses, and chronic inflammation, which may further contribute to oxidative stress, BaP-DNA adduct formation, and early carcinogenesis-related signaling abnormalities. Conversely, BaP-degrading gut bacteria may represent a potential intervention strategy for reducing BaP toxicity. Clarifying the interactions among BaP exposure, the gut microbiota, immune inflammation, and DNA damage may improve the assessment of the effects of long-term dietary BaP exposure on intestinal health and gastrointestinal cancer risk.
1151劉詠潔.pdf