title: Impact of dexrazoxane on doxorubicin-induced aneuploidy in somatic and germinal cells of male mice.
abstract: OBJECTIVE
  Despite dexrazoxane's increasing use in mitigating doxorubicin-induced cardiotoxicity, no data are available in the literature on the potential aneugenicity of drug combination. Therefore, detailed evaluation of aneugenic potential of this combination is essential to provide more insights into aneuploidy induction that may play a role in the development of secondary malignancies and reproductive toxicity after treatment with doxorubicin. Thus, our aim was to determine whether dexrazoxane has influence on the aneuploidy induced by doxorubicin in germinal and somatic cells of male mice.
  
  
  METHODS
  Sperm BrdU-incorporation assay, sperm FISH assay and the bone marrow micronucleus test complemented by FISH assay were used to determine aneuoploidy. Moreover, the formation of 8-OHdG, one of the oxidative DNA damage by-products, has been evaluated.
  
  
  RESULTS
  Dexrazoxane was not aneugenic at the doses tested. Pre-treatment of mice with dexrazoxane significantly reduced doxorubicin-induced aneuploidy in a dose-dependent manner. Doxorubicin induced marked biochemical alterations characteristic of oxidative DNA damage, and prior administration of dexrazoxane before doxorubicin challenge ameliorated this biochemical marker.
  
  
  CONCLUSIONS
  This study provides evidence that dexrazoxane has a protective role in the abatement of doxorubicin-induced aneuploidy. This activity resides, at least in part, in its radical scavenger activity. Thus, dexrazoxane can avert secondary malignancies and abnormal reproductive outcomes in cured cancer patients exposed to doxorubicin.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. attiasm@yahoo.com.|Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt. attiasm@yahoo.com.
authors.forename: S M
authors.initials: SM
authors.lastname: Attia
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: S F
authors.initials: SF
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: S A
authors.initials: SA
authors.lastname: Bakheet
mesh_terms: D000782:Aneuploidy; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D064730:Dexrazoxane / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D013094:Spermatozoa / Q000166:cytology* / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D064730:Dexrazoxane; D004317:Doxorubicin
keywords: Aneuploidy; Birth defects; Dexrazoxane; Doxorubicin; Oxidative DNA damage; Secondary malignancies