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
Wei, M.; Wanibuchi, H.; Morimura, K.; Salim, E.I.; Moku, M.; Doi, K.; Mitsuhashi, M.; Masuda, C.; Shen, J.; Kinoshita, A.; Fukushima, S.
Anticancer Research 24(2b): 785-790
2004
ISSN/ISBN: 0250-7005 PMID: 15161027 Document Number: 582401
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. Materials and 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. Conclusion: The present data indicate a lack of any inhibitory effects of FK228 on BBN-induced mouse urinary bladder carcinogenesis under the present conditions.