title: Gene expression profiling of di-n-butyl phthalate in normal human mammary epithelial cells.
abstract: Studies show that female workers in the personal-care industry have an increased risk of developing cancer believed to be the result of increased exposure to toxic and/or carcinogenic chemicals found in cosmetics, hair dyes, and nail polish. One chemical found in multiple personal-care products, di-n-butyl phthalate (DBP), is a known endocrine disruptor and has been found in increased levels in women of childbearing age. The goal of this study was to elucidate mechanisms of phthalate toxicity in normal human cells to provide information concerning interindividual variation and gene-environment interactions. Normal human mammary epithelial cell strains were obtained from discarded tissues following reduction mammoplasty [Cooperative Human Tissue Network (sponsors: NCI/NDRI)]. Gene transcription in each cell strain was analyzed using high-density oligonucleotide DNA microarrays (U133A, Affymetrix) and changes in the expression of selected genes were verified by real-time polymerase chain reaction (PCR) (ABI). DNA microarrays were hybridized with total RNA that was collected after DBP treatment for 5 hr and 10 hr. RNA was harvested from the vehicle control (acetone) at 10 hr. Data Mining Tool software (Affymetrix) was used to separate genes in clusters based on their expression patterns over time. Only 57 genes were found to be altered in all four cell strains following exposure to DBP. These included genes involved in fertility (inhibin, placental growth factor), immune response (tumor necrosis factor induced protein), and antioxidant status (glutathione peroxidase). Data from this study will help clarify the role of DBP in reproductive toxicity, and yield biomarkers of exposure for future epidemiology studies.
authors.affiliation: Molecular Epidemiology Team, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, MS L-3014, Morgan-town, WV 26505, USA.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Gwinn
authors.forename: Diana L
authors.initials: DL
authors.lastname: Whipkey
authors.forename: Lora B
authors.initials: LB
authors.lastname: Tennant
authors.forename: Ainsley
authors.initials: A
authors.lastname: Weston
mesh_terms: D002478:Cells, Cultured; D003993:Dibutyl Phthalate / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007265:Inhibins / Q000235:genetics / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D000072483:Placenta Growth Factor; D010968:Plasticizers / Q000494:pharmacology / Q000633:toxicity*; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C000608036:PGF protein, human; D010968:Plasticizers; D011257:Pregnancy Proteins; D014409:Tumor Necrosis Factor-alpha; D000072483:Placenta Growth Factor; D003993:Dibutyl Phthalate; D007265:Inhibins; D012313:RNA; D005978:Glutathione