| Objective:Silica dust,i.e.free silica dust,is the main causative agent of silicosis.The International Agency For Research on Cancer(IARC)has declared crystalline silica dust(quartz dust)as a class I carcinogen.However,the tumorigenic effects of silica dust on the body remain unclear,and many epidemiological studies have provided conflicting results.The aim of this study was to investigate the lung carcinogenic effect of silica dust in SD rats and to provide some theoretical basis for the lung carcinogenic effect of silica dust on the organism.Methods:The rats used for the experiments were 36 7-week-old healthy SD rats(Animal Experiment Center of Southern Medical University)free of specific pathogens(SPF grade).The rat silicosis model was constructed by tracheal drip injection of silica suspension.SD rats were randomly divided into a blank control group and a silica-stained group,with 6 rats in each group and 3 rats in each sex;3 time points were set for each group: 6 months,12 months and 24 months,respectively.The rat lung specimens were fixed with 4% paraformaldehyde,routinely paraffin-embedded and sectioned,and stained with hematoxylin eosin(HE)and Masson stain,respectively,to observe the histopathological changes of lung and to score Aschcroft pulmonary fibrosis.Rats were fasted for 8h,water fasted for 4h,fixed after anesthesia before examination,and scanned for single-layer spiral CT imaging of the lungs.Cell cycle and apoptosis levels were detected by flow cytometry.The altered expression levels of tumor markers in rats at different time points after silica dust toxicity staining were investigated by real-time PCR and Western blot.Dynamic observation of lung cancer caused by silica-stained SD rats and rats in the blank control group.Results:CT images showed: no cloudy high-density shadow in the 6-month control group;no cloudy high-density shadow in the 12-month control group;thickened lung texture in the 24-month control group;cloudy shadow and frosted granular shadow in the 6-month model group;enlarged mediastinal lymph nodes and calcification in the 12-month model group;and increased granular high-density shadow in the 24-month model group.In the12-month model group,the mediastinal lymph nodes were enlarged and calcified;in the24-month model group,the granular high-density shadow increased significantly,and the lesions were irregular and spherical in shape.The proportion of G0/G1 and S-phase cells in each group increased gradually over time,and the proportion of G2/M-phase cells decreased gradually.The gene expression levels and protein expression levels of CYFRA21-1 and NSE in rats were significantly increased after toxic transfection with silica particles(P<0.05),and the difference between groups was significant(P<0.05).The incidence and volume of tumors in rats increased significantly with the increase of the poisoning time,showing a certain time-effect relationship.There was no significant difference in the incidence of tumors in male and female rats,but the incidence of malignant lung squamous carcinoma in males(5.6%)> females(0%),lung adenocarcinoma in males(0%)< females(5.6%);the incidence of benign tumors thymoma in males(11.1%)> females(5.6%),the incidence of breast fibroadenoma male(0%)< female(11.1%),and the incidence of lipoma male(5.6%)> female(0%).Conclusion:As a causative agent of silicosis,silicon dioxide plays an important role in the pathogenesis of pulmonary fibrosis,silicosis nodules,and tumors in silicosis patients,and has some lung cancer-causing effects. |
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