title: Protection of mouse bone marrow from etoposide-induced genomic damage by dexrazoxane.
abstract: OBJECTIVE
  The objective of the current investigation is to determine whether non-toxic doses of the catalytic topoisomerase-II inhibitor, dexrazoxane, have influence on the genomic damage induced by the anticancer topoisomerase-II poison, etoposide, on mice bone marrow cells.
  
  
  METHODS
  The scoring of micronuclei, chromosomal aberrations, and mitotic activity were undertaken as markers of cyto- and genotoxicity. Oxidative damage markers such as reduced glutathione and lipid peroxidation were assessed as a possible mechanism underlying this amelioration.
  
  
  RESULTS
  Dexrazoxane pre-treatment significantly reduced the etoposide-induced micronuclei formation, chromosomal aberrations, and also the suppression of erythroblast proliferation in bone marrow cells of mice. These effects were dose dependent. Etoposide induced marked biochemical alterations characteristic of oxidative stress including enhanced lipid peroxidation and reduction in the reduced glutathione level. Prior administration of dexrazoxane ahead of etoposide challenge ameliorated these biochemical markers.
  
  
  CONCLUSIONS
  Based on our data presented, strategies can be developed to decrease the etoposide-induced genomic damage in normal cells using dexrazoxane.
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. attiasm@yahoo.com
authors.forename: Sabry M
authors.initials: SM
authors.lastname: Attia
authors.forename: Alaa A
authors.initials: AA
authors.lastname: Al-Anteet
authors.forename: Nouf M
authors.initials: NM
authors.lastname: Al-Rasheed
authors.forename: Abdulqader A
authors.initials: AA
authors.lastname: Alhaider
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Al-Harbi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects*; D002869:Chromosome Aberrations; D005047:Etoposide / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D018384:Oxidative Stress; D011929:Razoxane / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011929:Razoxane; D005047:Etoposide; D005978:Glutathione