Panx1 knockout promotes preneoplastic aberrant crypt foci development in a chemically induced model of mouse colon carcinogenesis.

Autor: Espírito Santo SG; Botucatu Medical School, Experimental Research Unit (UNIPEX), Multimodel Drug Screening Platform - Laboratory of Chemically Induced and Experimental Carcinogenesis (MDSP-LCQE), São Paulo State University (UNESP), Botucatu, São Paulo State, Brazil., Da Silva TC; School of Veterinary Medicine and Animal Science, Department of Pathology, University of São Paulo (USP), São Paulo, São Paulo State, Brazil., Cogliati B; School of Veterinary Medicine and Animal Science, Department of Pathology, University of São Paulo (USP), São Paulo, São Paulo State, Brazil., Barbisan LF; Botucatu Medical School, Experimental Research Unit (UNIPEX), Multimodel Drug Screening Platform - Laboratory of Chemically Induced and Experimental Carcinogenesis (MDSP-LCQE), São Paulo State University (UNESP), Botucatu, São Paulo State, Brazil.; Biosciences Institute, Department of Structural and Functional Biology, São Paulo State University (UNESP), São Paulo State, Brazil., Romualdo GR; Botucatu Medical School, Experimental Research Unit (UNIPEX), Multimodel Drug Screening Platform - Laboratory of Chemically Induced and Experimental Carcinogenesis (MDSP-LCQE), São Paulo State University (UNESP), Botucatu, São Paulo State, Brazil.; Biosciences Institute, Department of Structural and Functional Biology, São Paulo State University (UNESP), São Paulo State, Brazil.
Jazyk: angličtina
Zdroj: International journal of experimental pathology [Int J Exp Pathol] 2023 Dec; Vol. 104 (6), pp. 304-312. Date of Electronic Publication: 2023 Aug 18.
DOI: 10.1111/iep.12491
Abstrakt: Colorectal cancer, which is the third leading cause of cancer-related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel-forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1 -/- ) on the early events of chemically induced colon carcinogenesis in mouse. Wild type (WT) and Panx1 -/- female C57BL6J mice were submitted to a chemically induced model of colon carcinogenesis by receiving six intraperitoneal administrations of 1,2-dimethylhydrazine (DMH) carcinogen. Animals were euthanized 8 h (week 7) or 30 weeks (week 37) after the last DMH administration in order to evaluate sub-acute colon toxicity outcomes or the burden of ACF, respectively. At week 7, Panx1 genetic ablation increased DMH-induced genotoxicity in peripheral blood cells, malondialdehyde levels in the colon, and apoptosis (cleaved caspase-3) in colonic crypts. Of note, at week 37, Panx1 -/- animals showed an increase in aberrant crypts (AC), ACF mean number, and ACF multiplicity (AC per ACF) by 56%, 57% and 20%, respectively. In essence, our findings indicate that Panx1 genetic ablation promotes preneoplastic ACF development during chemically induced mouse colon carcinogenesis, and a protective role of Panx1 is postulated.
(© 2023 Company of the International Journal of Experimental Pathology (CIJEP).)
Databáze: MEDLINE
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