title: Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer.
abstract: BACKGROUND
  Genistein may be useful in the prevention or treatment of prostate cancer; however, it causes genetic damage in cultured human cells.
  
  
  OBJECTIVE
  The objective was to assess the potential genotoxicity of a purified soy unconjugated isoflavone mixture in men with prostate cancer.
  
  
  METHODS
  Twenty patients with prostate cancer were treated with 300 mg genistein/d for 28 d and then with 600 mg/d for another 56 d. In peripheral lymphocytes, DNA strand breaks were assessed as nuclear tail moment, chromosomal damage was assessed as micronucleus frequency (MF), and translocations of the MLL gene (11q23) were assessed by using fluorescence in situ hybridization. Values are also reported for 6 healthy men. The studies were performed under Investigational New Drug application no. 54 137 at a tertiary referral academic medical center.
  
  
  RESULTS
  No changes in group average or individual nuclear tail moment and MF were observed. We observed a single elevated MF value in one subject that exceeded a clinical threshold set before we initiated the study. A significant decrease in average COMET tail moment was observed on day 28 relative to day 0. We detected no genistein-induced rearrangements of the MLL gene in the 3 subjects we studied with this technique. MF increased significantly in lymphocytes exposed in vitro to unconjugated genistein at concentrations > or = 100 micromol/L. Total genistein never exceeded a peak concentration of 27.1 micro mol/L, and unconjugated genistein never exceeded a peak concentration of 0.32 micromol/L.
  
  
  CONCLUSIONS
  Although isoflavones are capable of inducing genetic damage in vitro, a similar effect was not observed in subjects treated with a purified soy unconjugated isoflavone mixture.
authors.affiliation: Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina, Chapel Hill 27599-7400, USA.
authors.forename: Woytek
authors.initials: W
authors.lastname: Miltyk
authors.forename: Corneliu N
authors.initials: CN
authors.lastname: Craciunescu
authors.forename: Leslie
authors.initials: L
authors.lastname: Fischer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Jeffcoat
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Koch
authors.forename: Wlodek
authors.initials: W
authors.lastname: Lopaczynski
authors.forename: Chrysa
authors.initials: C
authors.lastname: Mahoney
authors.forename: Robert A
authors.initials: RA
authors.lastname: Jeffcoat
authors.forename: James
authors.initials: J
authors.lastname: Crowell
authors.forename: Jennifer
authors.initials: J
authors.lastname: Paglieri
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D019833:Genistein / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007529:Isoflavones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008214:Lymphocytes / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000648:ultrastructure; D051788:Myeloid-Lymphoid Leukemia Protein; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011519:Proto-Oncogenes; D013025:Glycine max / Q000737:chemistry*; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; D007529:Isoflavones; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C004742:daidzein; C086566:glycitein; D019833:Genistein; D011495:Histone-Lysine N-Methyltransferase