Frequency of spontaneous and induced micronuclei in the peripheral blood of aging mice.

The mouse peripheral blood micronucleus assay, a measure of DNA damage in erythroblastic cells, was used to determine: (1) the incidence of spontaneously occurring micronucleated reticulocytes (MNRETs) as a function of age, and (2) the induction of micronuclei following treatment of young and old animals with mitomycin C. Male C57BL/6 mice, 92 weeks of age, exhibited a significantly higher frequency of spontaneously occurring peripheral blood MNRETs than mice that were 6 or 10 weeks of age. Mice that were 5-6 weeks or 91-92 weeks old were treated with one dose, or two consecutive doses of mitomycin C; this resulted in dose-related increases in the frequency of MNRETs. Mitomycin C, at a single dose of 1 or 2 mg/kg, induced one-third as many MNRETs in the older animals as compared to the younger animals. When treated with a split dose of mitomycin C (total dose 0.5 to 2 mg/kg), older animals displayed on average two-thirds the mutagenic response of the younger animals. However, analysis of variance performed on these data indicated that the age of the animals did not have a significant effect on their mutagenic response to mitomycin C at any dose level. It appears that aging mice may not be more sensitive to the mutagenic effects of chemically-induced DNA damage than younger mice, suggesting that the higher spontaneous mutation frequency in older mice could be the result of an increased load of accumulated DNA damage.