
-   Azoxymethane (AOM) protects intestinal stem cells and reduces crypt epithelial mitosis through a COX-1-dependent mechanism. AOM treatment (a DNA-damaging agent and intestinal carcinogen) increased COX-1 mRNA and protein expression. COX-1-derived PGE(2) synthesis may play a key role in the early phase of intestinal tumorigenesis in response to DNA damage [PMID: 17038629].
-   Treatment with aspirin or a COX-1 antisense oligonucleotide inhibits COX-1 activity/expression and suppresses tube formation in a system involving coculture of endothelial cells with colon carcinoma cells. COX-1 regulates angiogenesis in endothelial cells induced by colon cancer cells [PMID: 9630216].

## Summary

The PTGS1 gene encodes for an enzyme with dual cyclooxygenase and peroxidase activities, crucial in the biosynthesis of prostanoids from arachidonate [CS: 10]. In colon-related diseases and toxicities, the dysregulation of PTGS1 plays a significant role in modulating the inflammatory response and tissue repair processes [CS: 7]. For instance, in response to DNA damage or toxic events in the colon, such as exposure to a carcinogen azoxymethane (AOM), there is an upregulation of PTGS1, leading to increased synthesis of COX-1-derived PGE(2) [CS: 8]. This increase in PGE(2) synthesis might be a mechanism to protect intestinal stem cells and reduce crypt epithelial mitosis, crucial for maintaining intestinal integrity and facilitating repair processes [CS: 5]. However, this protective response can be maladaptive in the context of chronic inflammation or continuous exposure to carcinogens, as it inadvertently supports the proliferation of damaged or abnormal cells, contributing to the development and progression of colon cancer [CS: 6].
