The suitability of rat peripheral blood in subchronic studies for the micronucleus assay.
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.
Asanami
S
S
Naruto Research Institute, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan.
Shimono
K
K
Sawamoto
O
O
Kurisu
K
K
Uejima
M
M
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
D009153:Mutagens; D015122:Mercaptopurine; D010615:Phenacetin