The Change Of Expression Of Genes In Malignant Transformation Human Bronchial Epithelial Cells Induced By Glycidyl Methacrylate

Glycidyl methacrylate (GMA), as a comonomer in resin, is made for a wide application, inchluding coating, adhesive and plastic industries. There are two reactive functional groups: a very reactive epoxy group and an acrylic group. The product of GMA is brought together the chemical resistance of an epoxy with the weatherability of an acrylic due to its dual functionality.The metabolism of glycidyl methacrylate in mammals will likely proceed by at least two different and competing enzyme systems, epoxide hydratase and non-specific carboxylesterases. It has been previously reported that GMA is classified into the slight toxic category, with high irritation and immediate hypersensitivity and delayed hypersensitivity. The reproductive and development toxicity to rats has been also reported. Positive results are reported in several mutation assay. And it is capable of inducing malignant transformation in several types mammalia cells. Many results have demonstrated its carcinogenic potential.In vitro cell transformation test is an important way to study on carcinogenesis mechanism. 16HBE (human bronchial epithelial cells), an SV40 large T antigen-immortalized human airway epithelial cell line, retains the phenotype of the differentiated lineage of the parent. This cell line retains contact inhibition and rarely produces tumors when injected into nude mice, which provides us an ideal model for detecting carcinogenic potential of chemicals and for studying on the mechanisms of malignant transformation.In the study, biological characteristics of malignant transformation were dynamicly identified by the tests of conA and colony forming frequency on soft agar. The damage of chromosome in malignant transformation protophase cells and malignant transformation cells were observed dynamicly. The Agilent whole genome oligo microarray was used to detect the change of the expression of genes in malignant transformation protophase cells and malignant transformation cells induced by GMA, in order to discuss the mechanism of its potential carcinogenicity. 1 .Malignant transformation of humanbronchial epithelial cells induced by glycidylmethacrylate.It can be observed that the growth of cells induced by GMA is faster than the growth ofthe normal 16HBE cells through the growth curvature. The cells of 14^th generation intest group could be agglutinated in the conA solution. The transformed cells beinganchorage independence could grow in semi-solid agar. It is indicated that the rate ofchromosome structure aberration in malignant transformation protophase cells issignificative increased compared with the solvent control group (P<0.05); while themalignant transformation cells lack the normal nuclear style(P<0.05).2. Change of expression of genes in malignant transformation of 16HBE cells inducedby GMA.2.1 The list of changed expression genes in malignant transformation of 16HBE cellsinduced by GMA.There are 3667 genes showing different expression, including 2975 up-regulated genesand 692 down-regulated genes, in malignant transformation protophase cells. And 1789different expression genes was screened in the array, including 719 up-regulated genesand 1070 down-regulated genes, in malignant transformation cells. It was observed that283 genes expressed differently in both malignant transformation protophase cells andmalignant transformation cells. 88 of them showed up-regulation and 143 of themshowed down-regulation unanimously. 48 up-regulated genes and 4 down-regulatedgenes in malignant transformation protophase cells showed reverse trendecy inmalignant transformation cells.2.2Change of expression of several relative genes in malignant transformation of16HBE cells induced by GMA.The C19orf20, EPB49, PSCA, and RGS14 were observed up-regulated expression inthe malignant transformation protophase cells. The CENPF and CTGF were observeddown-regulated expression in the malignant transformation cells. The RASD1 wasobserved up-regulated expression in the malignant transformation protophase cellswhile down-regulated expression in the malignant transformation cells.2.3 Relative pathways with genes differently expressing in malignant transformation of 16HBE cells induced by GMA.There are 28 pathways in the malignant transformation protophase cells and 7 pathwaysin the malignant transformation cells expressing differently, with significative differencein statistics. And 3 pathways were observed significatively expressing differently inboth malignant transformation protophase cells and malignant transformation cells.As stated above, the malignant transformation of human bronchial epithelial cells is acomplicated process involved many genes,such as C19orf20, EPB49, PSCA, RGS1,CENPF , CTGF, and RASD1, in many pathways, such as signal transduction,cystoskeleton, infection, and so on.