Potential genotoxic effect of 186Re-HEDP on human lymphocyte cells: In-vitro evaluation with micronucleus-FISH analysis


Ozkal-Baydin P., GÜMÜŞ AKAY G., Varol N., RÜSTEMOĞLU A., Koroglu R., Yuksel S., ...Daha Fazla

Nuclear Medicine Communications, cilt.33, sa.4, ss.415-421, 2012 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 33 Sayı: 4
  • Basım Tarihi: 2012
  • Doi Numarası: 10.1097/mnm.0b013e3283505188
  • Dergi Adı: Nuclear Medicine Communications
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.415-421
  • Anahtar Kelimeler: fluorescence in-situ hybridization, genotoxic effect, human lymphocyte, micronucleus, Re-186-1,1-hydroxyethylidenediphosphonate, SITU HYBRIDIZATION, PERIPHERAL-BLOOD, PROSTATE-CANCER, BONE METASTASES, ANIMAL-MODEL, ASSAY, THERAPY, DAMAGE, DNA, RADIOSYNOVIORTHESIS
  • Ankara Üniversitesi Adresli: Evet

Özet

AIM: Systemic and local therapies can be used to treat painful bone metastases. It has been shown that certain pharmaceuticals such as Re (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 Re-1,1-hydroxyethylidenediphosphonate (Re-HEDP) on the cultured peripheral blood lymphocytes using an micronucleus (MN)-fluorescence in-situ hybridization assay. METHODS: Two lymphocyte cultures, with and without Re-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 Re-treated lymphocytes compared with the untreated group (P<0.001). The frequencies of centromere-positive [CEN(+)] and centromere-negative [CEN(-)] MN in the Re-treated and untreated groups were found to be similar; however, the ratio of CEN(-)/CEN(+) MN frequency was lower in Re-treated samples. CONCLUSION: These preliminary results support the idea that Re-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. Copyright © Lippincott Williams & Wilkins.