The role of TNF-α and NFkβ in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine

ABSTRACT

Purpose:

To analyze the potential of tumor necrosis factor-α (TNF-α) and factor nuclear kappa B (NF-κB) as colorectal cancer (CRC) biomarkers in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine (1,2-DMH).

Methods:

Twenty-four male Wistar rats were divided into two groups: sham and 1,2-DMH. First, 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. Histopathological analysis, immunohistochemistry, and gene expression of TNF-α and NF-κB were performed. Statistical analysis was performed using GraphPad Prism. The location of aberrant crypt foci (ACF) was analyzed by Kruskal-Wallis’ test. For analyses with two groups with parametric data, the t-test was used; for non-parametric data, the Mann-Whitney’s test was used. P < 0.05 was considered significant.

Results:

The number of ACF and macroscopic lesions was significantly higher (p < 0.5) in the 1,2-DMH group compared to the sham group, and most ACF were concentrated in the distal segment of the colon. There was a statistically significant increase (p < 0.5) in protein and gene expression of TNF-α and NF-κB in the 1,2-DMH group compared to the sham group.

Conclusions:

Our results provide supportive evidence that TNF-α and NF-κB pathways are strongly involved in CRC development in rats and might be used as early biomarkers of CRC pathogenesis in experimental studies.

Key words
Aberrant Crypt Foci; Carcinogenesis; Colorectal Neoplasms; Tumor Necrosis Factor-alpha; NF-kappa B