title: In vivo evaluation of the genotoxic effects of clomiphene citrate on rat reticulocytes: a micronucleus genotoxicity.
abstract: OBJECTIVE
  To determine the genotoxic effects of clomiphene citrate (CC) on rat reticulocytesin vivo.
  
  
  METHODS
  In this prospective, randomized, controlled study, rats were each assigned randomly to the CC 50, CC 100, CC 200, or control group and were given repeat doses of 0.16, 0.32 or 0.64 mg CC, or normal saline, respectively. Each study group received its CC dose in 2 ml of saline intraperitoneally for 5 days, while the control group received only 2 ml of saline. Each treatment cycle was repeated six times. Six months later, the rats were euthanized. Bone marrow tissues were removed, and pluripotent reticulocyte cells with micronuclei, nuclear buds, and binuclear abnormalities were analyzed using an in situmicronuclei assay under light microscopy. The proportion of micronucleated erythrocytes was measured.
  
  
  RESULTS
  Fewer cells with nuclear buds and binuclear abnormalities were detected in the CC 50 group and controls. The CC 100 and 200 groups had significantly (p < 0.05) more nuclear buds and binuclear abnormalities compared with the CC 50 group and controls in the cytogenetic analysis of bone marrow stem cells.
  
  
  CONCLUSIONS
  In rats, the micronucleus genotoxicity assay suggests a dose-dependent CC effect on genomic instability in bone marrow stem cells in vivo.
authors.affiliation: Department of Obstetrics and Gynecology, Cumhuriyet University, Faculty of Medicine, Sivas, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Duran
authors.forename: Ismail
authors.initials: I
authors.lastname: Ozdemir
authors.forename: Yeltekin
authors.initials: Y
authors.lastname: Demirel
authors.forename: Ozturk
authors.initials: O
authors.lastname: Ozdemir
authors.forename: Ali
authors.initials: A
authors.lastname: Cetin
authors.forename: Aysel
authors.initials: A
authors.lastname: Guven
mesh_terms: D000818:Animals; D002996:Clomiphene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005300:Fertility Agents, Female / Q000633:toxicity*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D051381:Rats; D017208:Rats, Wistar; D012156:Reticulocytes / Q000187:drug effects* / Q000473:pathology*; D013234:Stem Cells / Q000187:drug effects
chemical_list: D005300:Fertility Agents, Female; D002996:Clomiphene