| Abstract: | 許多流行病學研究指出，暴露二手煙及烹飪油煙為台灣女性罹患肺癌之危險因子。4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)及trans-trans-2,4-decadienal(DDE)分別是二手煙及烹飪油煙中被發現之致癌物或致突變物。Benzo[a]pyrene (BaP)是一種aryl hydrocarbon receptor (AhR) ligand，目前已被發現於二手煙及烹飪油煙中。本計劃目的為探討暴露二手煙及烹飪油煙對多環芳香烴類受器(AhR)，荷爾蒙受器表現(AR, ER, GR)及雌性素代謝之影響。我們以人類氣管上皮細胞BEAS-2B，女性肺腺癌細胞CL5及男性肺腺癌細胞NCI-H1355為研究材料，以real-time RT-PCR assay 及Western immunoblot方法分析BaP, NNK,DDE 對各種受器基因及蛋白表現之影響。目前我們已發現(1) BaP 在BEAS-2B and CL5細胞中活化AhR，進而增加CYP1A1 資料讀我檔案格式p15基因表現，但NNK and DDE無類似作用; (2) BEAS-2B and CL5細胞經BaP處理48小時後，AhR蛋白表現程度降低; (3)CL5細胞經BaP處理48小時後，女性荷爾蒙受器ERbeta 蛋白表現程度降低; (4)H1355細胞經BaP處理48小時後，男性荷爾蒙受器AR 蛋白表現程度降低。BaP 也減少BEAS-2B及H1355細胞之AR 基因表現; 但是NNK and DDE 對ERbeta 及AR 並無類似的作用; (5)BaP, NNK and DDE不會影響GR蛋白表現。以上結果顯示，BaP 可能經由降低AR and ERbeta表現，進而干擾性荷爾蒙對肺細胞之作用。
Exposure to environmental tobacco smoke (ETS) and cooking oil fume (COF) are suggested to be the risk factors of female lung cancer in Taiwan. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and trans-trans-2,4-decadienal (DDE) are respectively the abundant carcinogen/mutagen found in ETS and COF. In addition, benzo[a]pyrene (BaP), an ligand for aryl hydrocarbon receptor (AhR), is one of these carcinogens found in ETS and COF. In this project, we propose that exposure to ETS and COF may alter activity and expression of AhR and steroid hormone receptors and estrogen metabolism, and furthermore, these effects associate with lung carcinogenesis. We performed our evaluation with human immortalized bronchial epithelial cells BEAS-2B, female lung adenocarcinoma cells CL5 and male lung adenocarcinoma cell lines NCI-H1355. Gene and protein expression was respectively determined with real-time RT-PCR assay and Western immunoblot. The following results are found in the first period of projects. First, BaP activated AhR and induced CYP1A1 in BEAS-2B and CL5 cells. NNK and DDE had no significant effect on AhR activation. Second, BaP decreased AhR protein levels in BEAS-2B and CL5 cells 48 hr after treatment. Third, BaP reduced estrogen receptor beta (ERbeta) protein levels in CL5 cells 48 hr after treatment. Fourth, BaP reduced androgen receptor (AR) protein expression in H1355 cells 48 hr after treatment. AR gene expression was reduced by BaP treatment in BEAS-2B and CL5 cells. NNK or DDE alone had no similar effects on AhR, ERbeta and AR protein levels. Fifth, BaP, NNK and DDE do not change the levels of glucocorticoid receptor in these cell lines. These data suggest that BaP might interfere function of sex hormones in lung cells through the decrease in AR and ERbeta expression. We will further examine effects of BaP, NNK and DDE on sex hormones function in lung cells. |
