Influence of age and sex on the spontaneous DNA damage detected by Micronucleus test and Comet assay in mice peripheral blood cells

Abstract

We have investigated the normal variations in basal DNA damage detected by Comet assay in leukocytes and micronucleated erythrocytes (MNE) using the Micronucleus test (MN) in peripheral blood cells from 45 female and male mice from different age groups (newborns, 3.5, 12, and 104 weeks) to clarify age and sex-related changes. Comparison of basal DNA damage detected by Comet assay showed significantly increased values in 104 weeks old mice in relation to the other ages (P < or = 0.01), and newborn mice showed higher values in MNE frequency when compared to all the other groups (P < or = 0.01). A positive correlation was observed between Damage Frequency (r =0.382, P = 0.010) and Damage Index (r = 0.640, P < 0.001) and age. Age was also correlated with the ratio of polychromatic erythrocytes/normachromatic erythrocytes (PCE/NCE) (r = -0.473, P = 0.001), and the MNE frequency was positively correlated with the ratio of PCE/NCE (r = 0.454, P = 0.002). These results suggest an age-related slow down of DNA repair efficiency of DNA damage and/or DNA damage accumulation. Furthermore, data on the spontaneous MNE frequency indicate that the reticuloendothelial system matures with age, and there is a close relationship between erythropoiesis and micronucleus induction in erythrocytes. The influence of sex in the parameters analyzed was less clear. In conclusion, age seems to influence in basal DNA damage and should be considered in genotoxicity studies using mice. Finally, comparisons between assays must be made with care when different cells are compared (e.g. leukocytes and erythrocytes), as found with the Comet assay and MN test.

Effects of age on the frequency of micronuclei and degenerative nuclear abnormalities

“…They can also be caused by chemical reactions related to physiological processes. 9 In addition to age, studies have shown that differences in the occurrence of genetic damage can also be related to gender. [10][11][12] Trzeciak et al 11 reported that the removal of active carcinogens through tobacco is lower in women, thereby indicating biochemical differences between the genders.…”

Chromosome aberrations after high-dose 131I and 99mTc-MIBI administration using a micronucleus assay

“…Our results are in agreement with Joseph et al [19], who have stated an association between micronuclei and metastasis but no correlation with age or sex. However, Heuser et al [20] showed a positive relationship between spontaneous DNA damage in comet and micronuclei assays and age in mice.…”

Evaluation of drinking water treatment combined filter backwash water recycling technology based on comet and micronucleus assay

“…The Comet assay is used to detect primary DNA lesions (i.e., single or double strand breaks), while the MN assay is used to detect structural and numerical chromosomal damage. Additionally, the comet assay determines strand breaks and labile sites that are subsequently removed by repair enzymes (Heuser et al, 2008). In this study, both of the detecting techniques were successfully applied in detecting DNA damage in the two different drinking water treatment processes.…”