| ObjectTo observe the toxic effects of deoxynivalenol(DON),Cr,and As on mice,and to investigate the acute and chronic damage and potential of DON,Cr,and As in the liver,esophagus,stomach,and large intestine tissues of experimental animals.Carcinogenicity and possible combined pathogenic effects.Find clues related to the cause of esophageal cancer,provide a theoretical basis for disease prevention.MethodEpidemiological field investigations were conducted to collect grain samples from the high and low incidence areas of esophageal cancer in Dawen River Basin,and detect levels of DON and Pb.According to the test results,Cr,As and DON were selected to design animal experiments.Fifty male Kunming mice were randomly divided into five groups:blank control group,DON toxin group,elemental(As+Cr)group,low-dose combined-dose group(DON+As+Cr)and high-dose combined-dose.Group(DON+As+Cr).Each group of10 mice was housed in a single cage.Simulate natural feeding methods to infect the virus,that is,by spraying the appropriate concentration of toxin into the feed.The dose of toxin was: DON toxin,As,Cr of 200μg/kg.d for the single-dose group and the low-dose group,600μg/kg.d,As 1mg/kg.d,Cr 100 mg for the high-dose group./kg.d,the control group mice were ingested with the same batch of untreated common feed and kept for 50 days.After the end of the experimental period,liver,esophagus,stomach,and colon were taken for pathological examination.Serum was taken for tumor necrosis factor(TNF-α),vascular endothelial growth factor(VEGF),transforming growth factor(TGF-β1),and carbohydrate chain antigen.(CA19-9),squamous cell carcinoma antigen(SCCA),cy-tokeratin(CYRFA-21)detection.Result1.DON and element content: The average content of DON in flour samples in the high-incidence area of esophageal cancer was 373.68±53.63 ppb,and the mean lowincidence area was 163.75±32.45 ppb.The difference was significant(P<0.01).The average content of Cr in flour samples from high-incidence areas was 0.113±0.016mg/L,and the low incidence area was 0.056±0.006mg/L.The difference was statistically significant(P<0.05).The average content of as in flour samples from high-incidence areas was high.It was 0.036±0.005mg/L,and the low-incidence area was 0.002±0.001mg/L.The difference was statistically significant(P<0.05).The average content of Cd elements in the high-incidence flour samples was 0.108±0.003mg/L.The area was 0.002±0.001mg/L,and the difference was significant(P=0.01).The average Cu content in the high-incidence flour samples was 2.502±0.083mg/L,and the low incidence area was 2.106±0.144mg/L.Statistical significance(P<0.05).The difference in other elements between the two regions was not statistically significant.2.Histopathology showed no pathological changes in the liver of the blank control group;hepatic granulocyte degeneration and diffuse focal necrosis were observed in the liver of the DON-exposed mice;the result of liver sections in the As+Cr group was comparable to that of the DON.The poisoning group was similar;in the low-dose co-administered group(DON+As+Cr),the structure of the hepatic lobule was disordered,the degeneration of the hepatocytes was evident,the blood vessels in the portal area were expanded,fibrosis was developed and hepatic lobes were divided and divided;(DON+As+Cr)moderately diffuse diffuse edema of hepatocytes,palpebral dispersal in hyaline degeneration,focal multifocal necrosis,lymphocytic infiltration in portal area of necrosis.No significant pathological changes were found in the esophageal tissues of the blank control mice;esophageal sections of the DON-exposed mice showed local thickening of the epithelial stratum corneum;collagen fibers in the esophagus of the mice in the As+Cr group were thickened;and low-dose co-administered groups were used.(DON+As+Cr)mouse oesophageal mucosal inflammatory response is obvious;high-dose combination group(DON+As+Cr)mouse esophagus squamous epithelial dysplasia phenomenon,squamous epithelium light heterogeneous and arranged Mild disorders,mitotic figures in basal cells,thickening of the stratum corneum in some areas.There were no obvious pathological changes in gastric tissues of blank control group,DON-exposed group,and As+Cr group mice;a large amount of inflammatory cell infiltration was observed in the gastric mucosa of low-dose combination group(DON+As+Cr);In the poisoned group(DON+As+Cr),local epithelial necrotizing defects,parietal cells with diffuse diffuse edema,mild epithelial dysplasia of the pyloric stomach,and lymphocytic infiltration in the superficial epithelial connective tissue were observed.The pathological section of the colon of mice in the blank control group showed that the colonic mucosa layer was intact and no obvious pathological changes were observed;the mucus in the DON-exposed group was decreased,and the inflammatory cells infiltrated and the blood vessels were congested;the colon of the As+Cr group showed part of the colon section The normal structure disappeared,cell necrosis,chronic lymphocytic infiltration in the mucosal layer,and vascular congestion.In the low-dose combined-dose group(DON+As+Cr)mice,the glands were reduced,inflammatory cells infiltrated,and some epithelial cells were necrotic and detached.In the high-dose combination(DON+As+Cr)mouse colon,the necrosis of the intestinal epithelial necrosis was observed,the intestinal epithelial cells were slightly diverse,and the inflammatory cells infiltrated.3.Serum cytokine assay results: Compared with the blank control group(92.64±5.77-ng/L),the average content of serum TNF-α was 56.61±4.15ng/L.Significant(P<0.01);The average content of element group was 113.13±3.89ng/L,the average content of low-dose combination was 50.72±3.86ng/L,and the average content of high-dose combination was76.19±9.88ng/L The difference was statistically significant(P<0.01)The results of vascular endothelial growth factor(VEGF)test showed that the average content of VEGF in the control group was(261.81±34.22ng/L)compared with the control group(26.81±34.22-ng/L).395.35±43.16ng/L,the average content of element group was 643.65±56.48ng/L,the average content of low-dose combination group was 671.51±50.96ng/L,and the average content of high-dose combination group was 623.99±87.48ng/L,the difference was significant(P<0.01);the results of transforming growth factor(TGF-β2)showed that compared with the blank control group(263.79±36.28ng/L),the average content of DON exposure group It is 125.06±19.31ng/L,the average content of element group is356.78±28.82ng/L,low dose The average content of co-toxicity group was 110.55±16.16-ng/L,and the average content of high-dose co-administration group was 383.40±92.48ng/L.The difference was significant(P<0.01);the sugar chain antigen(CA19-9)The test results showed that compared with the blank control group(1.51±0.17U/ml),the average content of the DON exposure group was 3.01±0.31 U/ml,and the average content of the element group was 2.03±0.15U/ml.The average content of the poisoned group was 4.44±0.30 U/ml,and the average dose of the high-dose combination group was 5.50±0.78 U/ml.The difference was significant(P<0.01);the squamous cell carcinoma antigen(SCCA)The test results showed that compared with the blank control group(747.30±70.36ng/L),the average content of the DON-treated group was 473.82±37.69ng/L,and the average content of the element group was 1024.97±58.44ng/L.The average content of the poisoned group was418.14±35.74ng/L,and the average dose of the high-dose combination group was 545.56-±67.67ng/L,and the difference was significant(P<0.01).Cytokeratin(CYRFA-21)The results showed that the average content of the DON-treated group was 1.19 compared with the control group(2.37±0.27ng/ml).1.19±0.12ng/ml,the mean content of the element group was 3.53±0.26ng/ml,the average content of the low-dose combination was1.03±0.16ng/ml,and the average content of the high-dose combination was 4.60±1.01ng-/ml,the difference was significant(P<0.01).Conclusion1.DON toxin can cause liver cell granular degeneration,scattered focal necrosis,fibrous tissue hyperplasia in the portal area;can cause local thickening of the esophageal epithelial stratum corneum;can cause intestinal mucous cells in the colon to reduce the number of cells in a disorderly arrangement,intestinal Chronic inflammation of the mucous membranes,small blood vessels in the intestinal wall,congestion.2.Metals of As,Cr can cause hepatic liver cell granular degeneration,scattered focal necrosis;thickening of esophageal collagen fiber layer;can cause some of the normal structure of the colon to disappear,intestinal cell necrosis,chronic chronic lymphocytic infiltration of the mucosal layer,Vascular congestion in the intestinal wall.3.DON and metal Cr,As have a combined effect,can cause hepatic lobular structure disorder,hepatocyte ballooning,hepatocyte nucleus enlargement and deep staining with dysplasia,portal vein dilation,fibroplasia and divided around the liver Lobular;can cause esophageal submucosal vascular congestion,inflammatory response,epithelial thickening of the stratum corneum,squamous epithelial dysplasia,squamous epithelial light dysplasia and disorderly arrangement,basal cell mitotic figure;can cause local epithelial necrosis of the stomach Defects,diffuse edema of parietal cells,mild dysplasia of pyloric gastric foveal epithelium,intestinal gland reduction,necrosis of epithelial cells,abnormal cytoplasmic red staining,and inflammatory cell infiltration.After DON and metal Cr and As enter the body,they may interact with tumor necrosis factor(TNF),transforming growth factor(TGF-β1),squamous cell carcinoma antigen(SCCA),cytokeratin(CYRFA-21).The decrease of vascular endothelial growth factor(VEGF)and carbohydrate chain antigen(CA19-9).The higher content of DON and metal Cr and As in food may be one of the factors affecting the high incidence of esophageal cancer in Dawen River Basin of Shandong Province.There is a certain interaction between the two.5.The results suggest that long-term low-dose exposure to mycotoxins and heavy metal elements must attract sufficient attention. |
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