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: (I) the incidence of spontaneously occurring micronucleated reticulocytes (MNRETs) as a fun ction of age, and (2) the induction of micronuclei following treatment of young and old animals with mitomycin C. Male C57BL/6 mice, 92 week s 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 on e dose, or two consecutive doses of mitomycin C; this resulted in dose -related increases in the frequency of MNRETs. Mitomycin C, at a singl e dose of I 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 display ed 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 mut agenic response to mitomycin C at any dose level. It appears that agin g mice may not be more sensitive to the mutagenic effects of chemicall y-induced DNA damage than younger mice, suggesting that the higher spo ntaneous mutation frequency in older mice could be the result of an in creased load of accumulated DNA damage. (C) 1997 Elsevier Science B.V.