摘要
目的研究全氟辛烷磺酸(perfluorooctanesulfonate,PFOS)染毒对接种4T1乳腺癌细胞小鼠免疫状态的影响。方法将36只健康清洁级BALB/c雌性小鼠按体重随机分为3组,分别为对照(Tween-80)组及0.1、0.45 g/L PFOS染毒组,每组12只。采用自由饮水方式进行染毒,连续染毒56 d。染毒结束后,于小鼠右侧背部皮下注射2×10~5个4T1细胞,制作小鼠乳腺癌细胞荷瘤模型。通过real-time PCR方法检测小鼠Th1/Th2细胞因子IFN-γ和IL-4的mRNA表达水平;采用流式细胞术检测脾细胞中调节性T细胞(regulatory T cell,Treg)和髓样抑制性细胞(myeloid-derived suppressor cells,MDSC)的细胞分数。HE染色观察PFOS染毒对肿瘤组织的影响。结果与对照组相比,各浓度PFOS染毒组接种4T1乳腺癌细胞后小鼠脾细胞IFN-γmRNA表达水平升高,0.45 g/L染毒组小鼠脾细胞IL-4 mRNA表达水平升高,差异均有统计学意义(P<0.05)。与0.45 g/L PFOS染毒组相比,对照组和0.1 g/L PFOS染毒组小鼠接种4T1肿瘤细胞后脾细胞中MDSC的细胞分数均下降,差异均有统计学意义(P<0.05)。各组小鼠脾Treg细胞数量间比较,差异无统计学意义(P>0.05)。对照组和0.1、0.45 g/L PFOS染毒组荷瘤小鼠瘤块大小分别为(697.33±183.06)、(861.5±38.35)、(946.67±135.03)mm^3,各组间差异均无统计学意义(P>0.05);且肿瘤包块的大小随着PFOS染毒浓度的升高而呈增大趋势。0.45 g/L PFOS染毒组荷瘤小鼠肿瘤组织可见肿瘤细胞密集,核分裂较多,肿瘤血管更加丰富,与对照组比较,恶性程度更高。结论 PFOS染毒小鼠免疫状态向Th2型倾斜,接种4T1细胞后脾中MDSC的数量增多,肿瘤细胞恶性程度增加。
Objective To observe the immune state in BALB/c mice challenged with 4T1 breast cancer cell after PFOS exposure. Methods A total of 36 healthy female BALB/c mice were randomly divided into three groups according to body weight： the control group was administrated with Tween-80,the exposure groups were administrated with 0.1 g/L,0.45 g/L PFOS respectively,12 in each group,and the treatment were conducted through drinking water for 56 consecutive days. Once the exposure finished,the experimental murine model of breast cancer was prepared by subcutaneous injecting 4T1 cell line in the right back of the mouse. Real-time PCR was employed to detect the mRNA expression levels of Th1/Th2 typical cytokine IFN-γ and IL-4. Flow cytometry（FCM） were used to detect the ratios of regulatory T cells（Treg） and myeloid-derived suppressor cells（MDSC）. HE staining was used to observe the effect of PFOS on the cancer cells. Results Compared with the control group,in the spleen cells of the mice,the levels of IFN-γ mRNA increased significantly after 4T1 breast cancer cell challenge in all PFOS groups and the levels of IL-4 mRNA increased in the 0.45 g/L PFOS group（P〈0.05）. Compared with control group and the 0.1 g/L PFOS group,the ratio of MDSC increased obviously in the spleen cells in the 0.45 g/L PFOS group after 4T1 breast cancer cell challenge（P〈0.05）,while the ratio of Treg did not change obviously in all groups. The volumes of tumor in control,0.1 g/L PFOS and 0.45 g/L PFOS group were（697.33 ±183.06）,（861.5 ±38.35） and（946.67 ±135.03） mm-3 respectively（P〈0.05）. The size of tumor mass had an increasing tendence with the increase of PFOS concentration.Compared with the control group,0.45 g/L PFOS group showed a higher degree of malignancy with denser tumor cells,more mitosis and hypervascularization. Conclusion PFOS-exposed mice tends towards a Th2 dominant immune state type,the ratio of MDSC increases after 4T1 breast cancer cell challenge and the cancer cells showed a higher degr
出处
《环境与健康杂志》
CAS
北大核心
2016年第6期480-483,F0003,共5页
Journal of Environment and Health
基金
国家自然科学基金(81172630)
辽宁省自然科学基金(201202264)
关键词
免疫状态
全氟辛烷磺酸
乳腺癌
Immune state
Perfluorooctane sulfonate
Breast cancer
