title: Cigarette smoke inhibits endometrial epithelial cell proliferation through a nitric oxide-mediated pathway.
abstract: OBJECTIVE
  To determine the direct effects of cigarette smoke (CS) on human endometrial surface epithelial cell line proliferation.
  
  
  METHODS
  In vitro study using HES cells and primary human endometrial cells.
  
  
  METHODS
  University-based academic center.
  
  
  METHODS
  Premenopausal women in the proliferative phase of the cycle.
  
  
  METHODS
  The HES cells and primary human endometrial cells were exposed to cigarette smoke-saturated solution.
  
  
  METHODS
  Cell proliferation and expression of different isoforms of nitric oxide synthase.
  
  
  RESULTS
  Cigarette smoke inhibited HES cell proliferation in a dose- and time-dependant manner. The inhibitory effect of CS was blocked by hemoglobin and enhanced by L-arginine (L-Arg). Cigarette smoking and nicotine stimulated the expression of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) whereas benzo[a]pyrene (BP) only stimulated the expression of eNOS in HES cells. Cigarette smoke stimulated the expression of eNOS/iNOS in primary human endometrial cells, comprised of epithelial and stromal cells. The effect of CS on eNOS/iNOS expression in HES cells was blocked by ascorbic acid but not by glutathione.
  
  
  CONCLUSIONS
  Cigarette smoke inhibits endometrial cell proliferation through a nitric oxide-mediated pathway.
authors.affiliation: Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, California, USA. okhorram@obgyn.humc.edu
authors.forename: Omid
authors.initials: O
authors.lastname: Khorram
authors.forename: Guang
authors.initials: G
authors.lastname: Han
authors.forename: Thomas
authors.initials: T
authors.lastname: Magee
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005498:Follicular Phase; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D009538:Nicotine / Q000633:toxicity; D018722:Nicotinic Agonists / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017697:Premenopause; D015398:Signal Transduction / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors; D014026:Nicotiana
chemical_list: D000975:Antioxidants; D006454:Hemoglobins; D018722:Nicotinic Agonists; D012906:Smoke; D009569:Nitric Oxide; D001564:Benzo(a)pyrene; D009538:Nicotine; D001120:Arginine; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D005978:Glutathione; D001205:Ascorbic Acid