کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10900385 | 1084639 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Transcriptional signatures of environmentally relevant exposures in normal human mammary epithelial cells: benzo[a]pyrene
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کلمات کلیدی
NCIPAHSLRNHMecCHTNOligonucleotide arrays - آرایههای اولیگونوکلئوتیدBenzo[a]pyrene - بنزو [a] پییرنfold change - تغییر در برابرCarcinogenesis - سرطانزاییMammary cells - سلول های پستانNational Cancer Institute - موسسه ملی سرطانPolycyclic aromatic hydrocarbon - هیدروکربن آروماتیک چند حلقه ایPolycyclic aromatic hydrocarbons - هیدروکربن آروماتیک چندحلقهای
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Transcriptional signatures of environmentally relevant exposures in normal human mammary epithelial cells: benzo[a]pyrene Transcriptional signatures of environmentally relevant exposures in normal human mammary epithelial cells: benzo[a]pyrene](/preview/png/10900385.png)
چکیده انگلیسی
Changes in gene expression in a panel of primary normal human mammary epithelial cell strains, developed from healthy breast tissue obtained at reduction mammoplasty from different donors, in response to benzo[a]pyrene exposure have been investigated. It was expected that both gene expression changes common to cell strains derived from different donors as well as inter-individual variation would be observed. Therefore, the strategy that has been adopted is to identify potentially important changes, or useful changes from a biomonitoring perspective, using gene-array technology and a small number of donors; then investigate selected transcription responses using a large number of tissue donors and a cheaper method of transcript detection (real-time polymerase chain reaction). Here we report results from four primary normal human mammary epithelial cell strains that were treated with benzo[a]pyrene in vitro for either 6 or 24 h. Transcription was monitored using high-density oligonucleotide arrays (Affymetrix HuGeneFL). Total RNA was used for the preparation of labeled targets that were hybridized to microarrays containing probes representing more than 6800 human genes and expressed sequence tags. Gene expression data were analyzed using the GeneChip® software (MAS 5.0). Altered gene expression patterns were observed in response to benzo[a]pyrene in human mammary epithelial cell strains from different donors. Specifically, the dioxin inducible cytochrome P450 CYP1B1 was consistently induced in response to 6 and 24 h exposure to benzo[a]pyrene in cell strains from all four donors. Two other genes that were relatively consistently induced were IL1β and MMP1. Less consistent changes in other metabolism genes (CYP1A1, CYP11B2, and NQO1) and certain cell cycle control genes GOS2 and AF1Q were also induced, while EGR1 was suppressed. Although no change in p53 transcription was observed, an accumulation of p53 protein was detected using antibodies. A similar accumulation of Waf1 (p21) was also observed using immunohistochemistry, this was expected since p53 is p21's transcription factor. Significant inter-individual variations in both the levels and patterns of gene expression were observed, in response to benzo[a]pyrene exposure. These studies provide a complementary approach to molecular epidemiology for the investigation of differential susceptibility to chemical carcinogens, and specifically polycyclic aromatic hydrocarbons.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 221, Issue 2, 28 April 2005, Pages 201-211
Journal: Cancer Letters - Volume 221, Issue 2, 28 April 2005, Pages 201-211
نویسندگان
Channa Keshava, Diana Whipkey, Ainsley Weston,