The NTP conducts micronucleus tests in rats or mice, and the tissues most often assessed for frequency of micronuclei are bone marrow and peripheral blood. Micronucleus tests must be performed on cells that are dividing. The constant, rapid turnover of precursor cells makes erythrocytes an ideal cell type for a micronucleus test. Thus the bone marrow stem cells are continuously producing new erythrocytes to replace the ones that eventually die. If a stem cell has been damaged by a chemical and a micronucleus is formed as a consequence of this damage, the micronucleus remains in the cell and is very easy to observe microscopically.
Doses extend up to the maximum tolerated dose.
The route of administration in these short-term tests is usually either intraperitoneal injection or oral gavage. Based on the cell cycle and maturation times of the erythrocytes, harvesting of the bone marrow usually occurs 24 hours after the final dosing. The animals are killed by CO 2 inhalation and the femurs are removed. The bone marrow is flushed from the femurs and spread onto slides. In addition, the percentage of PCEs among the total erythrocyte population in the bone marrow is scored for each dose group as a measure of toxicity.