二甲基苯并蒽对肺肿瘤细胞P1—450基因表达的调节

Regulation of dimethylbenzanthracene-induced P1-450 gene expression in human lung tumor cells in culture]

Dimethylbenzanthracene (DMBA) stimulates expression of P1-450 gene in human lung tumor cells (ChaGo). 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. The methylation pattern of "-CCGG-" sequence of most of the coding region and of the 3' end of P1-450 gene is not affected by such DMBA treatment; DMBA-treatment of the cell induces hypomethylation of only the 5' end "-CCGG-" sequences of the gene. These results demonstrate that DMBA-treatment of ChaGo cells induced increased expression of gene can be correlated to the increased degree of site specific hypomethylation of the internal "-C-" residues of the "-CCGG-" sequences located at the 5' end of the P1-450 gene. However, it is also possible to have other molecular mechanism of regulation.