Micronuclei in circulating erythrocytes: a rapid screen for chromosomal damage during routine toxicity testing in mice.

Micronuclei in circulating erythrocytes provide a convenient measure of genetic damage resulting from chromosomal breakage or anaphase lag in bone marrow erythroblasts. The assay is easily integrated with acute, subchronic, or chronic toxicity tests. Scoring micronucleated erythrocytes in blood rather than bone marrow permits repeated sampling, simplifies sample preparation, and provides a more favorable cell population for scoring. Micronucleated erythrocytes accumulate during repeated exposures to clastogens and reach a maximum steady-state frequency after about five weeks of continuous treatment. Measurement of micronuclei in peripheral blood is therefore ideally suited for inclusion with routine subchronic toxicity tests. The same smear made for differential white blood cell counts at or near the end of the study can be scored for micronucleated erythrocytes, minimizing the effort required for this additional information and also permitting retrospective evaluation of completed studies.