The suitability of rat peripheral blood in subchronic studies for the micronucleus assay

Mutat Res. 1995 Jul;347(2):73-8. doi: 10.1016/0165-7992(95)90073-x.

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.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Erythrocytes / drug effects*
  • Erythrocytes / ultrastructure
  • Male
  • Mercaptopurine / toxicity
  • Micronucleus Tests / methods
  • Mutagens / toxicity*
  • Phenacetin / toxicity
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Mutagens
  • Mercaptopurine
  • Phenacetin