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Effect of acrolein, a lipid oxidation product, on the formation of the heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in model systems and roasted tilapia fish patties.

ABSTRACT: The effect of acrolein on the formation of the 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was investigated in a chemical model. Acrolein was found to increase PhIP formation at each tested addition level. 0-0.2 mmol of acrolein increased PhIP formation dose-dependently, while high levels of acrolein (>0.2 mmol) did not further increase PhIP formation. Mechanistic study showed that acrolein addition decreased the residue of phenylalanine and creatinine, but increased the content of some key intermediates. Further analysis indicated that acrolein can react with phenylalanine, creatinine, and PhIP to form adducts. These results suggested that acrolein was able to contribute to PhIP formation as a consequence of its comprehensive ability to facilitate Strecker degradation of phenylalanine and react with phenylalanine, creatinine, and PhIP. In addition, oxidation of the tilapia fish increased the PhIP formation in the roasted fish patties, further supporting the potential contribution role of lipid oxidation products to the formation of PhIP.

SUBMITTER: Jing M

PROVIDER: S-EPMC9237630 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a heterocyclic aromatic amine (HCA) formed in meat that is cooked at high temperatures and then ingested, can potentially be retained in human adipose tissues.MethodsTo determine if PhIP is bioactive in the adipocyte, we exposed a human adipocyte cell line,HepG2 and Caco-2 cells to low dose PhIP. Uptake and retention of PhIP was determined and cytotoxicity was assessed by the TUNEL assay. Relative expression of PhIP-activating genes (CYP1A1, CYP1A2, SULT1A1 and UGT1A1) was determined by RT-PCR and global expression changes were also examined.ResultsThe percent retention of 0.1 μCi [(14)C]-PhIP over a 24 h period was significantly higher in the adipocyte than the HepG2 (p = 0.0001) and Caco-2 (p = 0.0007) cell lines. Cytotoxicity rates were 14.4 and 2.6 % higher compared to controls in Caco-2 and HepG2 cells (p < 0.001 and 0.054, respectively); no significant differences were detected in adipocyte cells (p = 0.18). Caco-2 and HepG2 cells, respectively, had significantly higher basal expression of CYP1A1 (p = 0.001, p = 0.003), SULT1A1 (p = 0.04, p < 0.001) and UGT1A1 (p < 0.001, p = 0.01) compared to the adipocyte. Exposure to 5nM PhIP did not significantly induce expression of these genes in any of the cell lines. Global gene expression analysis of mature adipocytes exposed to 5nM PhIP for 72 h resulted in statistically significant changes in 8 genes (ANGPTL2, CD14, CIDEA, EGR1, FOS, IGFBP5, PALM and PSAT1). Gene-gene interaction and pathway analysis indicates that PhIP modulates genes controlled by the STAT3 transcriptional factor and initiates leptin signaling via the JAK/STAT and MAPK pathway cascades. Early growth response 1 (EGR1) and prostaglandin synthase 2 (COX-2) were down-regulated via c-Fos, while insulin binding protein 5 (IBP5) was up regulated. Expression of transcription factors (ANGPTL2, HP, LEP, SAA1, SAA2), genes related to inflammation (SAA1, LEP), diabetes (IGFBP5) and cancer risk (SAA2) were also elevated upon exposure to 5 nM PhIP..ConclusionsPhIP mediates gene expression changes within the adipocyte, and the pathways most affected are related to cancer and other chronic diseases. Further studies are needed on the relationship between dietary carcinogens such as PhIP with cancer, obesity and diabetes.

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Effect of acrolein, a lipid oxidation product, on the formation of the heterocyclic aromatic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in model systems and roasted tilapia fish patties.

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