title: The suitability of rat peripheral blood in subchronic studies for the micronucleus assay.
abstract: To examine the suitability of using rat peripheral blood from animals used in subchronic toxicity studies for micronucleus analysis, we orally administered phenacetin or 6-mercaptopurine for 14 days to groups of six rats and compared their micronucleus frequencies to the bone marrow micronucleus frequencies of rats similarly treated for only 2 days. In the 14-day test, phenacetin significantly increased the frequency of micronucleated reticulocytes in peripheral blood at 500 mg/kg starting from day 9, and at 750 and 1500 mg/kg starting from day 6; 6-mercaptopurine gave a positive response at 20 mg/kg starting from day 6. Positive responses in the bone marrow assay were obtained at the same dose levels. In the 2-day test, micronucleated polychromatic erythrocyte frequencies increased significantly at 1000 and 2000 mg/kg for phenacetin, and at 50, 100, and 200 mg/kg for 6-mercaptopurine. These results suggest that micronucleus assays using peripheral blood from rats in subchronic animal studies of phenacetin and 6-mercaptopurine are feasible and at least as sensitive for the assessment of micronuclei as an acute bone marrow micronucleus test.
authors.affiliation: Naruto Research Institute, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Asanami
authors.forename: K
authors.initials: K
authors.lastname: Shimono
authors.forename: O
authors.initials: O
authors.lastname: Sawamoto
authors.forename: K
authors.initials: K
authors.lastname: Kurisu
authors.forename: M
authors.initials: M
authors.lastname: Uejima
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D015122:Mercaptopurine / Q000633:toxicity; D015162:Micronucleus Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D010615:Phenacetin / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009153:Mutagens; D015122:Mercaptopurine; D010615:Phenacetin