title: 3-Aminobenzamide--a PARP inhibitor enhances the sensitivity of peripheral blood micronucleus and comet assays in mice.
abstract: BACKGROUND
  DNA repair is an essential outcome of DNA damage, which may compromise the end point of various in vitro and in vivo test systems of the genotoxicity evaluation. poly(ADP-ribose) polymerase (PARP) enzymes have an essential role in DNA repair. Here, we investigated the effect of 3-AB, a PARP inhibitor on the sensitivity of comet and PBMN assays.
  
  
  OBJECTIVE
  This study aimed to enhance the sensitivity of the comet and peripheral blood micronucleus (PBMN) assays using 3-aminobenzamide (3-AB), a well-characterized PARP inhibitor.
  
  
  METHODS
  Cyclophosphamide (CP, 50 mg/kg), 5-flourouracil (5-FU, 25 mg/kg), zidovudine (AZT, 400 mg/kg) and furosemide (FUR, 60 mg/kg) were selected as genotoxins. 3-AB was given every 8 h with the first dose given 2 h before the genotoxin treatment. For the PBMN assay, small amount of blood was taken from the tail tip of each animal and smears were prepared. The comet assay was performed in PBL, bone marrow and liver.
  
  
  RESULTS
  In the comet as well as PBMN assay, 3-AB pre-treatment enhanced the extent of DNA damage in all the combination groups (3-AB + CP, 3-AB + 5-FU and 3-AB + AZT) compared to CP, 5-FU and AZT per se. 3-AB also enhanced the DNA damage caused by FUR in the bone marrow and liver.
  
  
  CONCLUSIONS
  This study results clearly demonstrate that the pretreatment with 3-AB (30 mg/kg) significantly enhances the sensitivity of the PBMN and comet assays. This model may be useful for the detection of marginally active DNA damaging agents.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research , Mohali, Punjab , India .
authors.forename: Kamran
authors.initials: K
authors.lastname: Shekh
authors.forename: Sabbir
authors.initials: S
authors.lastname: Khan
authors.forename: Gopabandhu
authors.initials: G
authors.lastname: Jena
authors.forename: Bhavin R
authors.initials: BR
authors.lastname: Kansara
authors.forename: Sapana
authors.initials: S
authors.lastname: Kushwaha
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D020552:Comet Assay / Q000379:methods*; D003520:Cyclophosphamide / Q000633:toxicity; D005472:Fluorouracil / Q000633:toxicity; D005665:Furosemide / Q000633:toxicity; D008297:Male; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D015215:Zidovudine / Q000633:toxicity
chemical_list: D001549:Benzamides; D009153:Mutagens; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D015215:Zidovudine; D005665:Furosemide; C025160:3-aminobenzamide; D003520:Cyclophosphamide; D005472:Fluorouracil
keywords: DNA damage; genotoxicity; poly(ADP-ribose) polymerase; weak genotoxins