BaP诱导细胞恶性转化过程中DNA甲基化水平的变化

doi:10.3969/j.issn.1004-616x.2017.01.008

Abstract

Abstract:

OBJECTIVE: To investigate the role of DNA methylation as a possible mechanism of Benzo[a]pyrene (BaP) induction of malignant transformation in vitro. METHODS: Human bronchial epithelial cells (16HBE cell line) were treated with different concentrations BaP (0,10,20 and 40 μmol/L) for 1,9 and 15 weeks. Then,5-methylcytosine immunofluorescent assay was used to detect genomic DNA methylation level,Western blotting and RT-PCR were used to detect protein and mRNA levels of DNMT1,DNMT3a,DNMT3b and MBD2. RESULTS: BaP treatment decreased expression of 5-mC (methylation) in 16HBE cells in a dose- and time-dependent manner. The protein and mRNA levels of DNMT1 showed in a significant dose- and time-dependent reduction (P < 0.05),but there were no signi fi-cant changes in protein levels of DNMT3a,DNMT3b and MBD2(all P > 0.05). CONCLUSION: BaP treatment decreased the global DNA methylation levels in 16HBE cells and reduction of DNMT1 expression could play an important role.

Key words: benzo[a]pyrene, DNA methylation, malignant transformation

CLC Number:

R730.231

LIU Hailong, GAO Wei, GU Pan, DENG Yanxia, HUANG Xinfeng, WU Desheng, LIU Jianjun, HUANG Haiyan. Analysis of DNA methylation during BaP-induced malignant transformation in vitro[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(1): 42-45,50.

References

[1] MANOLI E,KOURAS A,KARAGKIOZIDOU O,et al. Polycyclic aromatic hydrocarbons (PAHs) at traffic and urban background sites of northern Greece:source apportionment of ambient PAH levels and PAH-induced lung cancer risk[J]. Environ Sci Pollut Res,2015,29(2):1-13.

[2] KAMAL A,MALIK R N,MARTELLINI T,et al. Exposure to dust-bound PAHs and associated carcinogenic risk in primitive and traditional cooking practices in Pakistan[J]. Environ Sci Pollut Res Int,2015,22(16):12644-12654.

[3] ROBERTSON K D. DNA methylation and human disease[J]. Nat Rev Genet,2005,6(8):597-610.

[4] 薛开先. 表遗传学推动新一轮遗传学的发展[J]. 遗传,2005,27(1):155-159.

[5] XUAN L I,XIYI L I,ZHILIANG ZHU,et al. Poly(ADP-ribose) glycohydrolase (PARG) silencing suppresses benzo(a)-pyrene induced cell transformation[J]. PLoS One,2016, 11(3):0151172.

[6] FEINBERG A P,TYCKO B. The history of cancer epigenetics[J]. Nat Rev Cancer,2004,4(2):143-153.

[7] ROBERTSON K D,WOLFFE A P. DNA methylation in health and disease[J]. Nat Rev Genet,2000,1(1):11-19.

[8] WIDSCHWENDTER M,JIANG G,WOODS C,et al. DNA hypomethylation and ovarian cancer biology[J]. Cancer Res, 2004,64(13):4472-4480.

[9] 蒋逸群,胡多沙,段芝,等. DNA甲基化、单核苷酸多态性与肿瘤[J]. 国际病理科学与临床杂志,2011,31(6):499-502.

[10] BAYLIN S B. DNA methylation and gene silencing in cancer[J]. Nat Clin Pract Oncol,2005,Suppl(1):4-11.

[11] KISSELJOVA N P,KISSELJOV F L. DNA demethylation and carcinogenesis[J]. Biochemistry (Mosc),2005,70(7):743-752.

[12] GRUNAU C,SANCHEZ C,EHRLICH M,et al. Frequent DNA hypomethylation of human juxtacentromeric BAGE loci in cancer[J]. Genes Chrom Cancer,2005,43(1):11-24.

[13] BAYLIN S B,ESTELLER M,ROUNTREE M R,et al. Aberrant patterns of DNA methylation,chromatin formation and gene expression in cancer[J]. Hum Mol Genet,2001,10(7):687-692.

[14] 杨林,鲁敏.DNA甲基化与肿瘤[J]. 中华医学研究杂志,2009,9(7):395-398.

[15] KONDO E,GU Z,HORⅡ A,et al. The thymine DNA glycosylase MBD4 represses transcription and is associated with methylated p16INK4a and hMLH1 genes[J]. Mol Cell Biol, 2005, 25(11):4388-4396.

[16] TUREK-PLEWA J,JAGODZINSKI P P. The role of mammalian DNA methyltransferases in the regulation of gene expression[J]. Cell Mol Biol Lett,2005,10(4):631-647.

[17] BACHMAN K E,ROUNTREE M R,BAYLIN S B. Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin[J]. J Biol Chem, 2001,276(34):32282-32287.

Analysis of DNA methylation during BaP-induced malignant transformation in vitro

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