Comparative study of 1,2-dimethylhydrazine and azoxymethane on the induction of colorectal cancer in rats

Abstract

a b s t r a c tThe induced colorectal carcinogenesis in rodents has a long history and currently uses the substances 1,2-dimethylhydrazine and azoxymethane.Objective: The aim of this study was to compare the inductive effect of the substances azoxymethane and 1,2-dimethylhydrazine in colorectal carcinogenesis.Method: 30 randomly chosen male Wistar rats were divided into four groups. G1 group was treated with 1,2-dimethylhydrazine and C1 was its control group; G2 group was treated azoxymethane and C2 was its control group. The animals were weekly weighed until euthanasia, when their intestines were removed, processed and analyzed by an experienced pathologist.Results: Among the control groups (C1 and C2) no histologic changes were observed; moderate dysplasia was detected in G2 group; hyperplasia, mild dysplasia, severe dysplasia and carcinoma were observed in G1 group. When this study compared the cost of the substances, 1,2-dimethylhydrazine was more than 50 times less expensive than azoxymethane.Conclusion: Azoxymethane is able to promote histological changes consistent with colorectal carcinogenesis. 1,2-Dimethylhydrazine produced neoplasia and dysplasia, and, compared to the azoxymethane, was more efficient in the induction of colorectal cancer. 168 j coloproctol (rio j). 2 0 1 4;3 4(3):167-173 Estudo comparativo das substâncias 1,2-dimetil-hidrazina e azoximetano na indução de câncer colorretal em ratos Palavras-chave: Câncer colorretal Modelo experimental Carcinogênese Azoximetano 1,2-Dimetil-hidrazina r e s u m o A carcinogênese colorretal induzida em roedores tem longa história e utiliza, atualmente, as substâncias 1,2 dimetil-hidrazina (DMH) e azoximetano (AOM). Objetivo: Comparar o efeito indutivo das substâncias AOM e DMH para o câncer colorretal (CCR). Método: 30 ratos Wistar machos foram randomizados em quatro grupos. O grupo G1 foi inoculado com DMH, o grupo C1 foi seu controle; G2 recebeu o AOM e C2 foi seu controle.Os animais foram pesados semanalmente até a eutanásia, quando tiveram seus intestinos retirados, processados e analisados por um patologista experiente.Resultados: Os animais dos grupos de controle apresentaram tecido colorretal normal e os animais do grupo G2 apresentaram um padrão de displasia moderada. Nas lâminas do grupo G1, foram encontradas regiões de hiperplasia, displasia leve, displasia grave, e carcinoma.Comparado o custo das substâncias AOM e DMH, este último teve um preço mais de 50 vezes menor ao do AOM.Conclusão: AOM é capaz de promover alteraç ões histológicas compatíveis com a carcinogê-nese colorretal. DMH produziu neoplasia e displasia grave e, comparada ao AOM, foi mais eficiente na indução do câncer colorretal.

Prevention of DNA damage and anticarcinogenic activity of Activia^® in a preclinical model

“…During the use, DMH was diluted in EDTA solution (0.37 mg/mL) with the same solution used as a vehicle for the control group treatment (Ishii et al, 2011;Mauro et al, 2013;Pesarini et al, 2013;Cantero et al, 2015;Navarro et al, 2015). DMH is an indirect trigger of colorectal carcinogenesis andone of the most used drugs in experimental models (Jucá et al, 2014).…”

Animal Models for Colorectal Cancer

“…Burlamaqui et al 4 stated that AOM is a more potent inducer than DMH because it is activated faster in the body. However, in a comparative study done by Jucá et al 12 it was observed that the induction by DMH promoted the appearance of dysplasias in mild, moderate and severe degree, in addition to carcinomas in situ, whereas the induction by AOM promoted only moderate dysplasia in the colon of the animals.…”

“…Individuals who develop familial adenomatous polyposis have a mutation in the APC (adenomatous polyposis of the colon) tumor suppressor gene, whereas those who develop hereditary nonpolyposis colorectal cancer have mutations in genes involved in DNA repair and mismatch repair (MMR) genes 6 . The sporadic form, in turn, is related to inflammatory bowel processes such as Crohn’s disease and ulcerative colitis, as well as to eating habits such as red meat consumption and low fiber intake 12 , 19 .…”

Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

“…17,18 Different from the other tumor models established by implanting tumor cells or tissues, the primary tumor is built through continual stimulation with chemical carcinogens over a long time period to induce neoplasms occurring spontaneously in the tissue of interest. 19,20 A recent study suggested that models of primary colorectal cancer are morphologically similar to human colon tumors. 20 If the complex pathophysiological processes of carcinogenesis of human colorectal tumors, involving the changes of cellular morphology and the expression of oncomarkers, can be simulated, it will be very helpful for realizing CRC detection and studies.…”