title: Combinatorial effect of zoledronic acid and irradiation on the prevention of DMBA-induced precancerogenic changes in the mammary tissues of rats.
abstract: BACKGROUND
  At present, the rates of breast cancer are continuously increasing, with over a million new cases being diagnosed worldwide each year. Hence, the development of new breast cancer chemopreventive drugs with acceptable efficacy and toxicity that are suitable for use for a protracted period of time is urgently needed. The present study investigated the potential preventive effects of zoledronic acid [ZOL] and radiotherapy [RT], both alone and in combination, on precancerogenic changes on the breast tissues of females.
  
  
  METHODS
  Wistar rats were treated with 7,12-dimethylbenz [a] anthracene [DMBA] at the acute phase. Fifty female rats were divided into seven groups: Control group [I]; ZOL, group [II]; RT, group [III]; DMBA, group [IV]; DMBA + RT, group [V]; DMBA + ZOL, group [VI]; and DMBA + ZOL + RT, group [VII].
  
  
  RESULTS
  The treatment of DMBA-exposed rats with ZOL and RT, both alone and in combination, successfully upregulates the transcriptional levels of Bax, caspase-3, caspase-9, p21, and BRCA 1 in mammary tissues, which may account for the elevated apoptotic activities observed and the eventual inhibition of tumor growth. The administration of RT and ZOL both alone and in combination was found to be effective for inhibiting the DMBA-induced precancerogenic changes on breast tissues and modulating the expression of apoptosis-associated proteins in the acute phase.
  
  
  CONCLUSIONS
  The combination of RT and ZOL was more effective than either agent alone. Our results suggest that the administration of ZOL and irradiation in combination can offer maximal protection against DMBA-induced mammary precancerogenic changes.
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, University of İnonu, Malatya, Turkey.
authors.forename: Simay
authors.initials: S
authors.lastname: G Rocak
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of İnonu, Malatya, Turkey.
authors.forename: Aysun Bay
authors.initials: AB
authors.lastname: Karabulut
authors.affiliation: Department of Biology, Faculty of Science, University of Fırat, Elazğ, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tuzcu
authors.affiliation: Department of Pathology, Faculty of Medicine, University of İnonu, Malatya, Turkey.
authors.forename: Nurhan
authors.initials: N
authors.lastname: Şahin
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, University of İnonu, Malatya, Turkey.
authors.forename: Öztun
authors.initials: Ö
authors.lastname: Temelli
authors.affiliation: Department of General Surgery, Faculty of Medicine, University of İnonu, Malatya, Turkey.
authors.forename: Volkan
authors.initials: V
authors.lastname: İnce
authors.affiliation: Department of Animal Nutrition, Faculty of Veterinary Science, University of Fırat, Elazğ, Turkey.
authors.forename: Kazim
authors.initials: K
authors.lastname: Şahin
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D019398:Genes, BRCA1; D007093:Imidazoles / Q000627:therapeutic use*; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000528:radiation effects; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D015127:9,10-Dimethyl-1,2-benzanthracene; D000077211:Zoledronic Acid