title: Inhibition of vascular cell growth by X-ray irradiation: comparison with gamma radiation and mechanism of action.
abstract: OBJECTIVE
  Catheter-based delivery of gamma and beta radiation effectively inhibits restenosis. Major disadvantages of these radioisotopes include continuous emission; excessive depth of penetration, creating safety hazards (gamma); and inadequate penetration, limiting effectiveness (beta). Low-voltage X-rays have a distinct potential advantage, because the source is active only when current is applied, and depth of penetration is voltage dependent. This study was performed to determine if low-voltage X-rays inhibit smooth muscle and adventitial cell growth in vitro and to determine the molecular mechanisms involved in this cellular response.
  
  
  RESULTS
  Vascular cells in culture were exposed to low-voltage X-ray radiation and analyzed for their subsequent ability to proliferate. X-ray irradiation caused a dose-dependent inhibition in proliferation, similar to the effect seen with equivalent doses of gamma radiation. The radiation-induced inhibition of proliferation did not appear to be related to apoptosis, but rather to delayed progression through the cell cycle, because a 65% increase in the proportion of cells in S phase was seen 24-96 h after X-ray exposure compared to control. Expression of p53, a cell cycle transcriptional activator, and p21, a cell cycle inhibitor, were significantly elevated after exposure to low-voltage X-rays, providing a potential mechanism for this delay.
  
  
  CONCLUSIONS
  Low-voltage X-rays can effectively inhibit proliferation of vascular smooth muscle and adventitial cells. This inhibition is apparently due to a delay in progression through the cell cycle, which is mediated by increases in the levels of cell cycle inhibitors.
authors.affiliation: Department of Medicine, Emory University, Atlanta, GA 30322, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Scott
authors.forename: I R
authors.initials: IR
authors.lastname: Crocker
authors.forename: Q
authors.initials: Q
authors.lastname: Yin
authors.forename: D
authors.initials: D
authors.lastname: Sorescu
authors.forename: J N
authors.initials: JN
authors.lastname: Wilcox
authors.forename: K K
authors.initials: KK
authors.lastname: Griendling
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D017209:Apoptosis / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014965:X-Rays
chemical_list: C493956:CDKN1A protein, human; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53