title: Role of melatonin and luzindole in rat mammary cancer.
abstract: BACKGROUND
  Recent studies have analyzed the efficacy of various agents in experimental chemoprevention trials. In our study, the effects of melatonin (Mel) and its antagonist Luzindole (Luz) on Heme oxygenase-1 (HO-1) in a NMU (N-methyl-N-nitrosourea)-induced rat mammary carcinoma model are investigated. We aim to demonstrate the relationship between Mel and HO-1.
  
  
  METHODS
  Spraque-Dawley rats were treated with NMU at age 55 days to induce mammary carcinoma. Forty-eight rats were divided into four groups consisting of: (a) physiological saline group (PSG); (b) control group, NMU is given; (c) Mel group (500 μg daily); (d) Mel antagonist Luz group (0.25 mg/kg/day i.p.). The animals were sacrificed; their serum and tissues were sampled for histopathologic evaluation, markers of endocrine derangement (serum prolactin, estradiol, and progesterone levels), apoptotic changes, DNA fragmentation, markers of oxidative stress and HO-1 immune expression were measured.
  
  
  RESULTS
  Most tumors developed in the Luz group (42%), followed by the control group (33%), and the Mel group (17%). The tumor latency was longer in Mel-treated group (control and Luz at week 17, Mel at week 21). The maximum tumor volume was also smaller in Mel group when compared to control and Luz groups (p < .05). In Mel group estradiol, progesterone, and prolactin levels were decreased compared to control group (p < .001; p < .01; and p < .01) and levels of apoptotic activity and DNA fragmentation ratio increased.
  
  
  CONCLUSIONS
  The increment of HO-1 expression with Mel is described; possible underlying mechanisms of these effects await further investigations.
authors.affiliation: Department of General Surgery, School of Medicine, Marmara University, Istanbul, Turkey. umitugurlu@gmail.com
authors.forename: Ugurlu M
authors.initials: UM
authors.lastname: Umit
authors.forename: Terzioglu
authors.initials: T
authors.lastname: Berna
authors.forename: Kaya
authors.initials: K
authors.lastname: Handan
authors.forename: Erbarut
authors.initials: E
authors.lastname: Ipek
authors.forename: Yegen
authors.initials: Y
authors.lastname: Berrak
authors.forename: Erzik
authors.initials: E
authors.lastname: Can
authors.forename: Gulluoglu M
authors.initials: GM
authors.lastname: Bahadir
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008770:Methylnitrosourea / Q000009:adverse effects; D018384:Oxidative Stress; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D014363:Tryptamines; C057154:luzindole; D011374:Progesterone; D004958:Estradiol; D008770:Methylnitrosourea; D011388:Prolactin; D051547:Heme Oxygenase-1; D008550:Melatonin