Abstract
Diets high in red meats, particularly meats cooked at high temperature, increase the risk of colon cancer due to a production of heterocyclic aromatic amines (HAAs). Of the identified HAAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most mass abundant colon carcinogen in charred meat or fish. Here, we comprehensively examined sex-dependent colon transcriptome signatures in response to PhIP treatment to identify biological discrepancies. Eight-week-old male and female C57BL/6N mice were intraperitoneally injected with PhIP (10 mg/kg of body weight) and colon tissues were harvested 24 h after PhIP injection, followed by colon transcriptomics analysis. A list of differentially expressed genes (DEGs) was utilized for computational bioinformatic analyses. Specifically, overrepresentation test using the Protein Analysis Through Evolutionary Relationships tool was carried out to annotate sex-dependent changes in transcriptome signatures after PhIP treatment. Additionally, the most significantly affected canonical pathways by PhIP treatment were predicted using the Ingenuity Pathway Analysis. As results, male and female mice presented different metabolic signatures in the colon transcriptome. In the male mice, oxidative phosphorylation in the mitochondrial respiratory chain was the pathway impacted the most; this might be due to a shortage of ATP for DNA repair. On the other hand, the female mice showed concurrent activation of lipolysis and adipogenesis. The present study provides the foundational information for future studies of PhIP effects on underlying sex-dependent mechanisms.
Highlights
Colorectal cancer is the third most common cancer worldwide, regardless of sex differences, and it is the 2nd most fatal cancer in the United States according to the most recent statistics data [1]
In 2020, approximately 150,000 new colorectal cancer diagnoses are expected in the United States, with more than 50,000 predicted deaths occurring in the same year [1]
Lists of differentially expressed genes (DEGs) for male and female groups were separately obtained based on the following cut-off criteria—fold change ≥1.2 and p-value < 0.05
Summary
Colorectal cancer is the third most common cancer worldwide, regardless of sex differences, and it is the 2nd most fatal cancer in the United States according to the most recent statistics data [1]. In 2020, approximately 150,000 new colorectal cancer diagnoses are expected in the United States, with more than 50,000 predicted deaths occurring in the same year [1]. Westernized diets have been linked to the incidence of colorectal cancer, the consumption of diets rich in meats. Cooking meats at high temperatures generates heterocyclic aromatic amines (HAAs), potent carcinogens [2,3,4]. Of the identified HAAs, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant HAA produced in charred meat and fish. PhIP and its early cancer markers, such as colonic PhIP-DNA adducts and aberrant crypt foci, have been widely utilized in various animal models for colon cancer studies (e.g., Reference [5])
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
