Experimental Epidemiology Studies On Pathogenic Effects Caused By DON And NOC

Objective:We carried out the subchronic animal experiments to oberserve morbigenous effects,which were caused by Dexoynivalenol(DON) and Nitrogen-nitroso compound (NOC).Our study mostly aimed to elucidate the effects they had on the digestive systems of the experimental animals and the effects of acute, chronic toxicity, as well as potential carcinogenic effects on the organs or tissues,such as oesophagus,stomach,liver and rectum of the experimental ainimals.This work might provide a basis theory for preventing digestive system carcinorma.Method:Experimental mice weaned 7 days were divided into four groups at random, there were 32 mice in each group,with females and males accounting for one half.Every mouse in DON group was given DON with the oral dose of 0.5mg/kg body weight a time, every mouse in NOC group was given NOC with the oral dose of 0.25 mg/kg body weight a time,every mouse in DON + NOC group was given DON with the oral dose of 0.5mg/kg and NOC with the oral dose of 0.25mg/kg body weight a time,control group was given isometrical physiological saline,two days a time.Sixty days later,all the mice were killed and the organs or tissues of oesophagus,stumach,liver and rectum were abtained.HE pathological slices of this organs were observed.In dddition,the concentration of DON in grain sanples in TaiAn was detected using HPLC-MS in order to explain the relationship between DON and the tumour.All the statistical analyses performed by the software of SAS9.0.Result:1.Poisonous effect on oesophagus tissue:Pathological changes of the oesophagus tissues were observed in the animals of the experimental groups,and the positive ratios in mammilla extension,the epithelium tissue corpora mammillaria accrementition,cellula epithelia vacuolization,accrementition of epithelium tissue parakeratosis were 34.04%,8.51%,8.51% and20.21%,respectively.The DON+NOC group had high positive ratio in mammilla extension, the epithelium tissue corpora mammillaria accrementition,accrementition of epithelium tissue parakeratosis,with 50.00%,15.63%,25.00%,respectively.The DON group had higher positive ratio in mammilla extension,with 32.26%.The NOC group had higher positive ratios in mammilla extension and accrementition of epithelium tissue parakeratosis,and the positive ratio was 19.35%,25.81%,respectively.However,the above changes were not observed in the control group.The difference in mammilla extension and accrementition of epithelium tissue parakeratosis were statistically significant between the experimental group and control group (P﹤0.05) according toχ2 test.2.Poisonous effect on stomach tissue:Pathological changes of stomach tissues,were also found in the experimental animals,the positive ratios in the polyp formation tendency,the gland mild heterotype,the epithelium tissue in deep lamella mild heterotype,the epidermis mucosae necrosis,necrosis of the gland,accrementition of epithelium tissue,and the Vessel expansion were 31.91%,29.79%,42.55%,40.43%,52.13%,13.83%,9.57%,respectively.The DON+NOC group had higher positive ratios in the polyp formation tendency,the epithelium tissue in deep lamella mild heterotype and the epidermis mucosae necrosis,the positive ratios were 46.88%,62.50%,59.38%, respectively.The DON group had higher positive ratios in the polyp formation tendency,the epithelium tissue in deep lamella mild heterotype,the epidermis mucosae necrosis, necrosis of the gland,and the positive ratios was 22.58%,29.03%,25.81% and 45.16%,respectively.The NOC group had higher positive ratios in the epithelium tissue in deep lamella mild heterotype,the epidermis mucosae necrosis,the necrosis of the gland,and the positive ratio was 38.71%,51.61% and 52.61%,respectively.Inflammation change was detected in every group.The difference in the polyp formation tendency,the epithelium tissue in deep lamella mild heterotype,the epidermis mucosae necrosis,the necrosis of the gland,the gland mild heterotype were statistically significant between experimental groups and control group(P﹤0.05)according toχ2 test.The difference in the epithelium tissue in deep lamella mild heterotype were statistically significant between the DON+NOC group and DON group (P﹤0.007).3.Poisonnous effect on liver tissue:Pathological changes of liver tissues were observed in the experimental groups,and the positive ratio in the large flap necrosis,the large flap fatty degeneration,the scrap fatty degeneration,the focal necrosis,the acidophilia changes,the focal heterotype,the inflammatory cell infiltration,the new born conjugate nuclear liver cell and the vessel expansion pathological changes were 7.45%,39.36%,22.34%,13.83%, 17.02%,17.02%, 76.60%,50%,31.91%,respectively.The DON+NOC group had higher positive ratios in the large flap necrosis(21.88%),the large flap fatty degeneration (65.63%),the focal necrosis (28.13%),the focal heterotype(25.00%),the new born conjugate nuclear liver cell(25.00%). The DON group had higher positive ratios in the large flap fatty degeneration and the focal heterotype,and the positive ratio was 22.58% and 25.81%,respectively.The NOC group had higher positive ratios in the large flap fatty degeneration pathological changes and the vessel expansion,and the positive ratios were 29.03% and 25.58% , respectively.However, pathological changes were also detected in the liver tissues in control group,and the positive ratio in the vessel expansion,the scrap fatty degeneration,the acidophilia changes,and inflammatory cell infiltration were 6.25%,75.00%,33.33% and 45.45%,respectively.The difference in the large flap necrosis,the large flap fatty degeneration,the focal necrosis,the focal heterotype,the new born conjugate nuclear liver cell and the vessel expansion pathological changes were statistically significant between the experimental groups and control group(P﹤0.05).The significant differences in the large flap fatty degeneration were also found between the DON+NOC group and control group(P﹤0.007).4.Poisonous effect on rectum tissue:Pathological changes of rectum organ tissues were observed in the experimental groups,and the positive ratios in the gland mild heterotype,the epithelium mucosae necrosis,the membrana propria inflammatory cell infiltration,the mucosae dropsy,the gland disorganization,the folliculus lymphaticus formation and the eosinophilic granulocyte infiltration pathological changes were 40.43%,43.62%,58.51%, 14.89%,8.51%, 23.40%,respectively.The DON+NOC group had higher positive ratios in the gland mild heterotype,the epithelium mucosae necrosis and the gland disorganization,and the positive ratios were 71.88%,46.88% and 18.75%,respectively.The DON group had higher positive ratios in the gland mild heterotype and the epithelium mucosae necrosis,and the positive ratioswere 9.03% and 32.26%,respectively.The NOC group had higher positive ratios in the gland mild heterotype,the epithelium mucosae necrosis and the gland disorganization,and the positive ratios were 19.35%,51.61% and 16.13%,respectively.Pathological changes were also found in control group and the positive ratios in the mucosae dropsy,the folliculus lymphaticus formation and the eosinophilic granulocyte infiltration pathological changes were 25.00%,3.13% and 3.13%.The differences in the gland mild heterotype,the gland disorganization,the epithelium mucosae necrosis,the eosinophilic granulocyte infiltration and the membrana propria inflammatory cell infiltration were statistically significant between the experimental groups and control group (P﹤0.05).In addition,the difference in the gland mild heterotype was also statistically significant between the DON+NOC and DON group(P﹤0.05).Furthermore,the difference in the gland mild heterotype was significant between the DON+NOC group and NOC group. 5.In addition,we detected the DON concentrations in the grain samples in TaiAn,the differences were statistically significant between the areas of higher incidence of oesophageal cancer and those with low incidence(P﹤0.05) .Conclusion:1.DON can induce precancerosis of the digestive system,such as the polyp formation tendency,the gland and epidermis mild heterotype,as well as acute and chronic pathology changes,such as the organ tissue necrosis,the inflammation dropsy and fatty degeneration,etc.2.NOC can also induce precancerosis of the digestive system,such as the polyp formation tendency and the gland and mammilla extension,as well as acute and chronic pathology changes,such as the organization necrosis,the inflammation dropsy denaturaation,big piece fatty degeneration,etc.3.The synergy of DON and NOC may cause digestive system acute and chronic pathology damages,such as,the appearances of necrosis , fatty degeneration and inflammation dropsy,etc.Moerever they also induce precancerosis,such as,the polyp formation tendency and the gland,epidermis heterotype.The above pathological changes were more obvious than DON or NOC were given alone.4.The concentration of DON were higher in grains samples collected from areas with higher incidence of oesophagus than those with lower incidence in Taian.5.Our results indicated:DON,NOC obvious damaged the digestive system.At the same time,they had the latent carcinogenic effects,and there effects obvious synergism.