摘要
苯并[a]芘(B[a]P)和人乳头瘤病毒(HPV)均是导致人类癌症的重要因素,前者是环境中广泛存在的致癌物,后者可诱导皮肤和黏膜鳞状上皮细胞异常增殖进而诱发癌症。流行病学证据表明烟草烟气与HPV协同作用可促进口咽鳞癌、头颈部鳞状细胞癌和肺癌等恶性肿瘤的发生,然而关于HPV与多环芳烃(PAHs)的协同致癌作用机制尚不明确。通过平板克隆形成实验、细胞划痕实验以及细胞侵袭实验对B[a]P和HPV的协同致癌作用进行了研究,比较了经B[a]P处理后人宫颈癌He La细胞(HPV阳性)和C33A细胞(HPV阴性)表型的变化;用高效液相色谱-电喷雾串联质谱(HPLC-ESI-MS/MS)法对B[a]P导致的主要DNA加合物——二氢二醇环氧化物-N2-脱氧鸟苷(BPDE-N2-d G)进行了定量分析。结果表明,浓度为10μmol/L的B[a]P能够显著促进He La和C33A细胞的侵袭和克隆形成能力,且呈剂量效应关系;经B[a]P处理后He La细胞的侵袭和克隆形成能力均显著高于C33A细胞(p<0. 01),并显著高于对照组He La细胞(p<0. 01)。经浓度为10μmol/L的B[a]P处理后He La细胞及C33A细胞中BPDE-N2-d G水平均最高,分别为(4 172±124) fmol/mg DNA和(1 255±228) fmol/mg DNA;且各B[a]P处理浓度下的He La细胞中BPDE-N2-d G的水平均显著高于C33A细胞(p<0. 01),证明了HPV能显著促进B[a]P对DNA的损伤作用,为进一步揭示B[a]P和HPV的协同致癌作用提供了依据。不仅为B[a]P和HPV相关癌症的防治提供了新策略,而且将为癌症病因学研究提供新的方法。
Both benzo[a]pyrene(B[a]P)and human papillomavirus(HPV)are important factors inducing human cancer.The former is a carcinogen widely found in the environment,and the latter can induce cancer by resulting in abnormal proliferation of cutaneous and mucosal squamous cells.Epidemiological evidence suggests that tobacco smoke and HPV can synergistically promote the development of malignant tumors such as oropharyngeal squamous cell carcinoma,head and neck squamous cell carcinoma and lung cancer.However,the mechanism of the synergistic carcinogenesis of HPV and PAHs is unclear.Cell colony formation assay,cell scratch assay and cell invasion assay were conducted to assess the synergistic carcinogenesis of HPV and B[a]P,and the cell phenotypic changes of the human cervical carcinoma HeLa cells(HPV positive)and C33A cells(HPV negative)exposed to B[a]P.High performance liquid chromatography-electrospray tandem mass spectrometry(HPLC-ESI-MS/MS)was used to quantitatively determine the main DNA adduct caused by B[a]P,dihydroglycol epoxide-N2-deoxyguanosine(BPDE-N2-dG).The results showed that the ability of cells invasion and colony formation of HeLa and C33A were significantly promoted by 10μmol/L B[a]P with a dose-response relationship.The invasion and colony formation of B[a]P-treated HeLa cells were significantly higher than those of C33A cells(p<0.01)and those of HeLa cells without B[a]P treatment(p<0.01).The group treated with 10μmol/L B[a]P in HeLa cell and C33A cell induced the highest levels of BPDE-N2-dG,4 172±124 fmol/mg DNA and 1 255±228 fmol/mg DNA,respectively.The levels of BPDE-N2-dG in HeLa cells treated with B[a]P were significantly higher than those in C33A cells(p<0.01).These combined results suggest that HPV could effectively promote DNA damage induced by B[a]P,which provide a reasonable explanation for the results of cellular experiments described above.It provides not only a new strategy for the prevention and treatment of B[a]P and HPV-related cancer,but also a new method for cancer etiology research
作者
庄琢琛
贾帅楠
李劲涛
崔鑫
孙国辉
Pramod Upadhyaya
赵丽娇
钟儒刚
ZHUANG Zhuo-chen;JIAShuai-nan;LI Jin-tao;CUI Xin;SUN Guo-hui;UPADHYAYA Pramod;ZHAO Li-jiao;ZHONG Ru-gang(Beijing KeyLaboratory of Environmental and Viral Oncololgy,College of Life Science and Bio-Engineering,Beijing University of Technology,Beijing100124,China;Masonic Cancer Center,University of Minnesota,Minneapolis55455,United States)
出处
《化学试剂》
CAS
北大核心
2019年第10期1002-1010,共9页
Chemical Reagents
基金
国家自然科学基金资助项目(21778011)
北京市长城学者支持计划项目(CIT&TCD20180308)
北京市教委重点实验室项目(PXM2015_014204_500175)
北京市自然科学基金资助项目(7184192)
中国博士后基金资助项目(2017M620567)
北京博士后基金资助项目(2018-ZZ-022)
