Regulation of P1-450 Gene Expression by Dimethylbenzanthracene in Human Lung Tumor Cells in Culture  

作　　者：费云标 Kirstin L.Brown Debajit K.Biswas 

机构地区：[1]Institute of Developmental Biology,Academia Sinica,Beijing 100080 [2]Harvard School of Dental Medicine and Harvard Medical School,Boston,Mass 02115 U.S.A. [3]Laboratoory of Molecular Biology,Harvard School of Dental Medicine and Harvard Medical School,Boston,Mass 02115 U.S.A.

出　　处：《Developmental and Reproductive Biology》1992年第1期7-15,T001-T003,共12页发育与生殖生物学报（英文版）

基　　金：This work is supported by grant(HL32034) from the U.S.National Institute of Heart,Lung and Blood.

摘　　要：Polycyclic aromatic hydrocarbons(PAHs),dimethyl beazanthracene(DMBA)and benzo-(a)-pyrene(BaP),stimulate the expression of the P1-450 gene in human lung tumor cells(ChaGo)in culture.A concentration-and time-dependent increase in the level of P1-450 specific mRNA sequences hasbeen observed in ChaGo cells treated with sublethal concentrations of DMBA.Results presentedsuggest that the parent compound causes the induction of P1-450 gene expression.The methylationpattern of the internal“-C-” residues of the “-CCGG-” sequence has been studied in a stretch ofabout 8000 base pairs(bp)of DNA sequence in and around the P1-450 gene in the control andDMBA-treated ChaGo cells.A comparative Southern blot analysis of the Msp Ⅰ/Hpa Ⅱ digestedDNA of the control and DMBA-treated ChaGo cells followed by hybridization with ^(32)P-labelledregion-specific probes,revealed that i)the internal “-C-” residues of the “-CCGG-” sequences ofdifferent regions of P1-450 gene were methylated to different degrees;ii)DMBA treatment of thecells induced hypomethylation of only the 5' end “-CCGG-” sequences of the gene;and iii)themethylation patterns of “-CCGG-” sequences of most of the coding region and of the 3' end regionof P1-450 gene were not affected by such DMBA treatment.Polycyclic aromatic hydrocarbons(PAHs),dimethyl beazanthracene(DMBA)and benzo-(a)-pyrene (BaP),stimulate the expression of the P1-450 gene in human lung tumor cells(ChaGo)in culture. A concentration-and time-dependent increase in the level of P1-450 specific mRNA sequences has been observed in ChaGo cells treated with sublethal concentrations of DMBA.Results presented suggest that the parent compound causes the induction of P1-450 gene expression.The methylation pattern of the internal“-C-” residues of the “-CCGG-” sequence has been studied in a stretch of about 8000 base pairs(bp)of DNA sequence in and around the P1-450 gene in the control and DMBA-treated ChaGo cells.A comparative Southern blot analysis of the Msp Ⅰ/Hpa Ⅱ digested DNA of the control and DMBA-treated ChaGo cells followed by hybridization with ^(32)P-labelled region-specific probes,revealed that i)the internal “-C-” residues of the “-CCGG-” sequences of different regions of P1-450 gene were methylated to different degrees;ii)DMBA treatment of the cells induced hypomethylation of only the 5' end “-CCGG-” sequences of the gene;and iii)the methylation patterns of “-CCGG-” sequences of most of the coding region and of the 3' end region of P1-450 gene were not affected by such DMBA treatment.

关 键 词：P1-450 gene Dimethyl-benzanthracene(DMBA) METHYLATION HYPOMETHYLATION 

分 类 号：R734.2[医药卫生—肿瘤]