An Integrative Approach to Characterize the Early Phases of Dimethylhydrazine-Induced Colorectal Carcinogenesis in the Rat
Rita Silva-Reis,
Catarina Castro-Ribeiro,
Mariana Gonçalves,
Tiago Ferreira,
Maria João Pires,
Carlos E. Iglesias-Aguirre,
Adrián Cortés-Martín,
María V. Selma,
Juan Carlos Espín,
Elisabete Nascimento-Gonçalves,
Alexandra Moreira-Pais,
Maria J. Neuparth,
Francisco Peixoto,
Eduardo Rosa,
Adelina Gama,
Rita Ferreira,
Paula A. Oliveira,
Ana I. Faustino-Rocha
Affiliations
Rita Silva-Reis
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Catarina Castro-Ribeiro
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Mariana Gonçalves
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Tiago Ferreira
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Maria João Pires
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Alexandra Moreira-Pais
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Maria J. Neuparth
Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto, 4200-450 Porto, Portugal
Francisco Peixoto
Chemistry Research Center, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Eduardo Rosa
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Adelina Gama
Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Rita Ferreira
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Paula A. Oliveira
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
Ana I. Faustino-Rocha
Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
This study aimed to characterize an animal model of colorectal cancer (CRC) in the early stages of disease development. Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2), receiving EDTA–saline injections and two induced groups (CRC1 and CRC2), receiving 1,2-dimethylhydrazine (DMH) injections for seven consecutive weeks. CRC1 and CTRL1 were euthanized at the 11th week, while CRC2 and CTRL2 were euthanized at the 17th week. DMH treatment decreased microhematocrit values and IL-6, ghrelin, and myostatin serum levels. Histopathological analysis of intestinal sections showed that DMH-treated rats were characterized by moderate to severe epithelial dysplasia. An adenoma was observed in one animal (CRC2 group), and the presence of inflammatory infiltrate at the intestinal level was primarily observed in DMH-treated animals. DMH also induced Ki-67 immunoexpression. The gut microbiota analysis showed a higher abundance of Firmicutes, Clostridia, Clostridiales, Peptostreptococcaceae, Blautia, Romboutsia, and Clostridium sensu stricto in CRC than CTRL rats, whereas Prevotellaceae, Prevotella, Akkermansia, and Lactobacillus levels were more prevalent in CTRL animals. Our results suggest that this model could be helpful to investigate chemoprevention in the early stages of CRC.