Morphological Changes and Inflammation Preceded the Pathogenesis of 1,2-Dimethylhydrazine-Induced Colorectal Cancer

• Published in: Asian Pacific journal of cancer prevention : APJCP Vol. 25; no. 6; pp. 2059 - 2067
• Main Authors: Adrianto, Albertus Ari, Riwanto, Ignatius, Sadhana, Udadi, Setyawan, Henry, Mahati, Endang, Widyarini, Sitarina, Wandita, Afranetta Aulya Asri, Paramita, Dewi Kartikawati
• Format: Journal Article
• Language: English
• Published: Thailand West Asia Organization for Cancer Prevention 01.06.2024
• Subjects: 1,2-Dimethylhydrazine - toxicity; Aberrant Crypt Foci - chemically induced; Aberrant Crypt Foci - metabolism; Aberrant Crypt Foci - pathology; Adenocarcinoma - chemically induced; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; Carcinogens - toxicity; Colon - metabolism; Colon - pathology; Colorectal Neoplasms - chemically induced; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cyclooxygenase 2 - metabolism; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - pathology; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Male; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha - metabolism; dimethylhydrazine; aberrant crypt foci; Cyclooxygenase-2; CRC; tumor necrosis factor-&alpha
• ISSN: 1513-7368; 2476-762X
• DOI: 10.31557/APJCP.2024.25.6.2059

This study examined the morphological changes in the colonic mucosa and the presence of inflammation in rats induced with 1,2-dimethylhydrazine (DMH) 30 mg/kg BW over 9, 11, and 13 weeks without a latency period. Hematoxylin and eosin staining was performed to assess the morphology and characteristic alteration of the epitheliocytes in the colon. Immunohistochemistry was employed to assess the expression of tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2). The difference in the severity of inflammation and COX-2 expression was examined using one-way analysis of variance. The correlation of COX-2 expression with the severity of inflammation was analyzed using Spearman's rank correlation test. Until week 13, chronic inflammation and non-hyperplastic and hyperplastic aberrant crypt foci occurred. The severity of inflammation gradually shifted from high moderate to low moderate. TNF-α expression was high in all groups; however, COX-2 expression was gradually lower with longer duration of induction, which corresponded with the severity of inflammation. DMH induction until week 13 without a latency period caused chronic inflammation without the formation of adenoma or adenocarcinoma. A very strong correlation was established between COX-2 expression and inflammation.