title: Potential genotoxic effect of 186Re-HEDP on human lymphocyte cells: in-vitro evaluation with micronucleus-FISH analysis.
abstract: OBJECTIVE
  Systemic and local therapies can be used to treat painful bone metastases. It has been shown that certain pharmaceuticals such as 186Re (rhenium-186) are effective in the treatment of pains caused by bone metastasis and a correlation between bone metastases and T cells has also been shown. The aim of this study was to investigate the genotoxic effect of 186Re-1,1-hydroxyethylidenediphosphonate (186Re-HEDP) on the cultured peripheral blood lymphocytes using an micronucleus (MN)-fluorescence in-situ hybridization assay.
  
  
  METHODS
  Two lymphocyte cultures, with and without 186Re-HEDP, were set up from 20 healthy individuals. MN frequencies were determined by a classical cytokinesis-blocked micronucleus assay and samples with the highest MN frequencies were used for fluorescent in-situ hybridization analyses with the 'all human centromeres' probe.
  
  
  RESULTS
  Our results show a significant increase in the MN frequency in 186Re-treated lymphocytes compared with the untreated group (P<0.001). The frequencies of centromere-positive [CEN(+)] and centromere-negative [CEN(-)] MN in the 186Re-treated and untreated groups were found to be similar; however, the ratio of CEN(-)/CEN(+) MN frequency was lower in 186Re-treated samples.
  
  
  CONCLUSIONS
  These preliminary results support the idea that 186Re-HEDP is a highly genotoxic radiopharmaceutical and shows a proaneugenic effect. Causing genotoxicity in lymphocytes, especially in T cells, that regulate bone metastases and tumor growth in bone, might be a mechanism of this pharmaceutical to reduce the pain of patients.
authors.affiliation: Department of Medical Biology, Ankara University Faculty of Medicine, Ankara, Turkey. ozkal@medicine.ankara.edu.tr
authors.forename: Pinar
authors.initials: P
authors.lastname: Ozkal-Baydin
authors.forename: Güvem
authors.initials: G
authors.lastname: Gümüş-Akay
authors.forename: Nuray
authors.initials: N
authors.lastname: Varol
authors.forename: Aydin
authors.initials: A
authors.lastname: Rüstemoğlu
authors.forename: Reyhan
authors.initials: R
authors.lastname: Köroğlu
authors.forename: Selcen
authors.initials: S
authors.lastname: Yüksel
authors.forename: Ozlem
authors.initials: O
authors.lastname: Küçük
authors.forename: Gülseren
authors.initials: G
authors.lastname: Aras
authors.forename: Erkan
authors.initials: E
authors.lastname: Ibiş
authors.forename: Asuman
authors.initials: A
authors.lastname: Sunguroğlu
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000150:complications / Q000532:radiotherapy / Q000556:secondary; D012968:Etidronic Acid / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000494:pharmacology / Q000633:toxicity*; D010146:Pain / Q000209:etiology / Q000532:radiotherapy; D011868:Radioisotopes / Q000633:toxicity*; D055815:Young Adult
chemical_list: D009942:Organometallic Compounds; D011868:Radioisotopes; C101598:rhenium-186 HEDP; D012968:Etidronic Acid