title: Mutagenic and clastogenic properties of (3-[3-(6-benzoyloxy-3-cyano-2- pyridyloxycarbonyl) benzoyl]-1-ethoxymethyl-5-fluorouracil) (BOF-A2), a new 5-fluorouracil derivative with anti-tumour activity.
abstract: As part of the safety assessment of (3-[3-(6-benzoyloxy-3-cyano-2- pyridyloxycarbonyl)benzoyl]-1-ethoxymethyl-5-fluorouracil) (BOF-A2), a new 5-fluorouracil (5-FU) derivative with anti-tumour activity, its potential genotoxicity was studied in 3 different tests. BOF-A2 was negative in a reverse mutation (Ames) test in strains of S. typhimurium and E. coli. BOF-A2 induced chromosomal aberrations in Chinese hamster cells in vitro especially in the presence of exogenous metabolic activation, and was clastogenic in vivo, inducing micronuclei in mouse bone marrow. The clastogenic activity of BOF-A2 was similar to that of 5-FU.
authors.affiliation: Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shibahara
authors.forename: E
authors.initials: E
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Awogi
authors.forename: G
authors.initials: G
authors.lastname: Tsushimoto
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: R R
authors.initials: RR
authors.lastname: Marshall
authors.forename: D J
authors.initials: DJ
authors.lastname: Kirkland
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000648:ultrastructure; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000633:toxicity; D066298:In Vitro Techniques; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D009153:Mutagens; C053194:Emitefur; D005472:Fluorouracil