title: Pre-pubertal exposure of cytarabine-induced testicular atrophy, impaired spermatogenesis and germ cell DNA damage in SD rats.
abstract: BACKGROUND
  Cytarabine (Ara-C) is an effective chemotherapeutic drug for the treatment of acute leukaemias. It inhibits the DNA synthesis and repair, thereby causes cytotoxicity in the proliferating cells.
  
  
  OBJECTIVE
  This study was aimed to investigate the effects of pre-pubertal exposure of Ara-C on testesticular development in juvenile SD rats and their function at puberty.
  
  
  METHODS
  Ara-C was injected at the doses of 50, 100 and 200 mg/kg/day from postnatal day (PND) 29-42 (14 days) by intraperitoneal (i.p.) route. Half of the animals were sacrificed on PND 43 and remaining on PND 70. End points of the evaluation included gross pathological examination, histomorphometric analysis, sperm count and sperm head morphology, cell proliferation and DNA damage as well as apoptosis analysis.
  
  
  RESULTS
  Ara-C treatment significantly decreased food and water intake, weight gain, testes and epididymis weight and increased histological alterations in the seminiferous tubule. Furthermore, Ara-C treatment significantly decreased the PCNA-positive cells and sperm count in a dose-dependent manner. Ara-C treatment also increased the DNA damage and apoptosis in testes and sperm as evident from the comet and TUNEL assays results.
  
  
  CONCLUSIONS
  The present study results clearly indicated that Ara-C treatment impaired spermatogenesis and adversely affects the testicular development and its function in rats by reducing the germ cell proliferation and the inducing DNA damage and apoptosis.
authors.affiliation: Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies, National Institute of Pharmaceutical Education and Research , S.A.S. Nagar, Punjab , India.
authors.forename: Ramana C
authors.initials: RC
authors.lastname: Namoju
authors.forename: Sabbir
authors.initials: S
authors.lastname: Khan
authors.forename: Ronak S
authors.initials: RS
authors.lastname: Patel
authors.forename: Firdos Y
authors.initials: FY
authors.lastname: Shera
authors.forename: Priyanka P
authors.initials: PP
authors.lastname: Trivedi
authors.forename: Sapana
authors.initials: S
authors.lastname: Kushwaha
authors.forename: G B
authors.initials: GB
authors.lastname: Jena
mesh_terms: D000818:Animals; D003561:Cytarabine / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000473:pathology
chemical_list: D003561:Cytarabine
keywords: Apoptosis; DNA damage; cytarabine; juvenile rat; spermatogenesis; testes