title: Lack of preventive efficacy of FK228, a histone deacetylase inhibitor, against N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder carcinogenesis in p53+/- and p53+/+ mice.
abstract: BACKGROUND
  The efficacy of FK228, a histone deacetylase inhibitor that is currently under early clinical trials for cancer therapy, against N-butyl-N-(4-hydroxybutyl)- nitrosamine (BBN) -induced mouse urinary bladder carcinogenesis was examined.
  
  
  METHODS
  Heterozygous p53-deficient (p53+/-) and wild-type (p53+/+) mice were given FK228 (0, 0.01 and 0.1 mg/kg i.p., 3 times/week, respectively) after 10 weeks of 0.05% BBN treatment, and were sacrificed at 22 and 24 weeks after the start, respectively.
  
  
  RESULTS
  There was no significant difference in the incidence of urinary bladder tumors among groups in the p53+/- or p53+/+ mice, although the high dose of FK228 increased the p21WAF1 mRNA expression in urinary bladder cancers in animals of both genotypes.
  
  
  CONCLUSIONS
  The present data indicate a lack of any inhibitory effects of FK228 on BBN-induced mouse urinary bladder carcinogenesis under the present conditions.
authors.affiliation: Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Morimura
authors.forename: Elsayed I
authors.initials: EI
authors.lastname: Salim
authors.forename: Masaharu
authors.initials: M
authors.lastname: Moku
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Doi
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: Chikayoshi
authors.initials: C
authors.lastname: Masuda
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.forename: Anna
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D047630:Depsipeptides; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D016159:Tumor Suppressor Protein p53; D002085:Butylhydroxybutylnitrosamine; C087123:romidepsin