Morphological and Molecular Alterations in 1,2 Dimethylhydrazine and Azoxymethane Induced Colon Carcinogenesis in Rats

The dimethyhydrazine (DMH) or azoxymethane (AOM) model is a well-established, well-appreciated, and widely used model of experimental colon carcinogenesis. It has many morphological as well as molecular similarities to human sporadic colorectal cancer (CC), which are summarized and discussed in this paper. In addition, the paper combines present knowledge of morphological and molecular features in the multistep development of CC recognized in the DMH/AOM rat model. This understanding is necessary in order to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH/AOM rat colon carcinogenesis. The DMH/AOM model provides a wide range of options for investigating various initiating and environmental factors, the role of specific dietary and genetic factors, and therapeutic options in CC. The limitations of this model and suggested areas in which more research is required are also discussed

Gastric emptying in rats with gastroduodenal disease induced by N-methyl-N-nitro-N-nitrosoguanidine and alcohol

The rate of gastric emptying was measured with a dye dilution technique in rats treated with N-methyl-N-nitro-N-nitrosoguanidine and alcohol. Gastric emptying was compared in rats with gastroduodenal inflamatory diseases and gastroduodenal neoplasms, and in those without gastroduodenal disease. Gasttric emptying was found to be significantly increased following the intragastric injection of liquid meal in rats with gastroduodenal diseases as opposed to the control group of healthy rats. These findings suggest than an increased gastric emptying of liquids can be explained by abolition on the relaxation of the gastric wall in rats with gastroduodenal diseases

Vpliv spola na indukcijo debeločrevesnega karcinoma z 1,2-dimetilhidrazinom (DMH) pri podganah Wistar

Human colorectal carcinoma appears more frequently in males. The aim of our study was to evaluate the influence of gender on the induction of colorectal carcinoma by 1,2-dimethylhydrazine (DMH) in Wistar rats. Sixty Wistar rats (30males, 30 females) were subjected to weekly subcutanous injections of DMH (20 mg/kg) for 15 weeks. After 25 weeks from the beginning of the experiment the animals were sacrificed and autopsied. All macroscopical lesions were evaluated histologicaly. Induction of colorectal tumors succeeded in 37% of males and 17% of females. There were 21 tumors of the large bowel found, of these 15 in males and 6 in females. Histologically, males had 11 adenomas, 2 signet-cell carcinomas and 2 adenocarcinomas, while females had 4 signet-cell carcinomas and 2 adenomas. We also found extracolonic tumors, mainly those of the small intestine and of the Zymbal glands. Wistar rats showed lower incidence of DMH-induced colorectal tumors in comparison with other strains ofrats. The gender-dependent difference in the incidence of colorectal tumors was found to be statistically marginally significant (p<0.08), whereas the difference in the incidence of all induced tumors between genders was significant (p<0.02). Males showed a greater incidence of coloreactal tumors and also a greater histological resemblance to human colorectal tumors than females. That is why we recommend Wistar males rather than females for research on colorectal tumors.Pri ljudeh je karcinom debelega črevesa pogostejši pri moških. Namen naše raziskave je oceniti vpliv spola na indukcijo debeločrevesnega karcinoma z 1,2-dimetilhidazinom (DMH) pri podganah Wistar. Uporabili smo 60 podgan seva Wistar (30 samcev, 30 samic), ki so jim 1-krat tedensko podkožno vbrizgali 20 mg DMH/kg telesne teže. Injicirali smo 15-krat. Po 25-ih tednih od začetka poskusa smo živali žrtvovali in jih obducirali. Vse makroskopske lezije smo histološko ovrednotili. Indukcija debeločrevesnih tumorjev je uspela pri 37% samcev in pri 17% samic. Našli smo 21 tumorjev debelega črevesa in danke: 15 tumorjev pri samcih in 6 pri samicah. Histološko smo pri samcih našli 11 adenokarcinomov, 2 pečatnocelična karcinoma in 2 adenoma, pri samicah pa 4 pečatnocelične karcinoma in 2 adenoma. Našli smo tudi tumorje izven debelega črevesa, predvsem tumorje tankega črevesa in Zymbalovih žlez. Podgane seva Wistar so v primerjavi z nekaterimi drugimi sevi podgan kazale manjšo pojavnost kolorektalnih tumorjev po indukciji z DMH. Razlika med spoloma v pojavnosti tumorjev v debelem črevesu in danki se je pokazala kot statistično majna (p < 0,08), statistično značilno razliko med spoloma pa smo ugotovili v pojavnosti vseh induciranih tumorjev (p < 0,02). Samci so kazali večjo incidenco kolorektalnih tumorjev, ki so bili tudi histološko bolj podobni tumorjem pri človeku. Zato priporočamo za raiskovalno delo na kolorektalnih tumorjeih Wistar samca

Dextran Sodium Sulphate Colitis Mouse Model: Traps and Tricks

Inflammatory bowel disease (IBD) is a complex multifactorial disease of unknown etiology. Thus, dozens of different animal models of IBD have been developed in past decades. Animal models of IBD are valuable and indispensable tools that provide a wide range of options for investigating involvement of various factors into the pathogenesis of IBD and to evaluate different therapeutic options. However, the dextran sulphate sodium (DSS-) induced colitis model has some advantages when compared to other animal models of colitis. It is well appreciated and widely used model of inflammatory bowel disease because of its simplicity. It has many similarities to human IBD, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using DSS model. As demonstrated in the present paper, various factors may affect susceptibility to DSS-induced lesions and modify results

Effect of the type of application of Newcastle disease virus on the Ehrlich ascites tumor

Newcastle disease virus (NDV) has been shown to have an inhibitory effect on the tumours. Most authors use peritumoral application of virus. The purpose of our studz was to compare the effects of the ip in contrast to sc application of the virus on the ip and sc transplanted Ehrlich ascites tumor (EAT) in CBA/H mouse. We measured the length of survival, the tumor cure rates, the metastatic rate, and the frequencz of ascites and sc tumors in the site of ip EAT injection. Prolongation of survival after the therapy with NDV in ip transplanted EAT average time of survival in control group was 70.5 days, and 107 and 79.9 days with ip and sc NDV virus therapy respectively. The differences were significant only between control group and the group treated with ip application of NDV. Tumor cure rates were: ipNDV group 30%, scNDV group 20% and control group 5%. NDV therapy in sc transplanted EAT prolonged the time of survivalin control group it was 63.3 days, and 75.2 and 65.9 days with ip and sc NDV therapy respectively. NDV therapy inhibited metastatic rate of ip transplanted EAT. Inhibition was more effective with ip application of NDV. VIrus therapz also lowered the frequencz of appearance of ascites and sc tumour in the site of ip EAT injevtion. In sc transplanted EAT ip application of NDV inhibited the metastatic rate while in sc applied NDV some stimulation of metastasation was found. Ip application of NDV was found to be superior in contrast to sc application in all its therapeutic effects against EAT. Our results show that the tumor inhibition of NDV, in the system we used, has the characteristics of the biological response modifiers

Polish Academy of Sciences

Effects of high-fat mixed-lipid diet and exercise on the antioxidant system in skeletal and cardiac muscles of rats with colon carcinom

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment

<div><p>The very effective anticancer drug doxorubicin (DOX) is known to have cardiotoxic side effects, which could be accompanied by autonomic modulation. Autonomic disbalance might even be an initiating mechanism underlying DOX-induced cardiotoxicity and can be studied noninvasively by the analysis of heart rate variability (HRV). A number of strategies have been assessed to predict chemotherapy-induced cardiac dysfunction while HRV, a potential detecting tool, has not yet been tested. Thus, we aimed to determine the effect of DOX treatment on HRV in a rat model of colorectal cancer. While pretreatment with fullerenol (Frl) acts protectively on DOX-induced cardiotoxicity, we aimed to test the effect of Frl pretreatment on DOX-induced HRV alterations. After the induction of colorectal cancer, adult male Wistar rats were treated with saline (n = 7), DOX (1.5 mg/kg per week, n = 7) or DOX after pretreatment with Frl (25 mg/kg per week, n = 7) for three weeks (cumulative DOX dose 4.5 mg/kg). One week after treatment rats were anaesthetized, standard ECG was measured and HRV was analyzed in time and frequency domain. During autopsy the intestines and hearts were gathered for biochemical analysis and histopathological examination. DOX treatment significantly decreased parasympathetically mediated high-frequency component (p<0.05) and increased the low-frequency component of HRV (p<0.05), resulting in an increased LF/HF ratio (p<0.05) in cancerous rats. When pretreated with Frl, DOX-induced HRV alterations were prevented: the high-frequency component of HRV increased (p<0.01), the low-frequency decreased (p<0.01), LF/HF ratio decreased consequently (p<0.01) compared to DOX only treatment. In all DOX-treated animals, disbalance of oxidative status in heart tissue and early myocardial lesions were found and were significantly reduced in rats receiving Frl pretreatment. Autonomic modulation accompanied the development of DOX-induced cardiotoxicity in rat model of colorectal cancer and was prevented by Frl pretreatment. Our results demonstrated the positive prognostic power of HRV for the early detection of DOX-induced cardiotoxicity.</p></div