Assessment of cytogenetic damage by quantitation of micronuclei in human peripheral blood erythrocytes.

The incidence of micronuclei (Howell-Jolly bodies) in peripheral blood erythrocytes of splenectomized and nonsplenectomized humans was evaluated as an index of genotoxic exposure. Subjects with intact spleens had very low frequencies of micronucleated cells among circulating erythrocytes, even when these individuals were exposed to known clastogenic agents used in cancer therapy (no micronuclei were seen in 100,000 cells). After splenectomy, the frequency of micronuclei among erythrocytes of untreated subjects rose slowly and after 4 mo established a steady-state level of approximately 2.0/1000, a value similar to that reported for human bone marrow (Goetz et al. Relationship between experimental results in mammals and man: cytogenetic analysis of bone marrow injury induced by a single dose of cyclophosphamine. Mutat. Res., 31: 247-254, 1985; and Hogstedt et al. Micronuclei and chromosome aberrations in bone marrow cells and lymphocytes of humans exposed mainly to petroleum vapors. Hereditas, 94: 179-187, 1981. Chemotherapy increased these levels, with individual samples from patients on daily treatment often having values greater than 5 times higher than control levels. The frequency of micronucleated erythrocytes rose as the duration of clastogenic exposure increased and returned to near base-line levels approximately 4 mo after treatment was discontinued. These findings suggest that it will be possible to use analyses of circulating erythrocytes to assess genotoxic exposures among splenectomized human populations. The ease of sample preparation and scoring should make it possible to monitor individuals with greater statistical power than is feasible with conventional cytogenetic techniques.