Comparison of alkaline single cell gel (Comet) and peripheral blood micronucleus assays in detecting DNA damage caused by direct and indirect acting mutagens

Abstract

The alkaline single cell gel (SCG) or `comet' and peripheral blood micronucleus (pbMN) assays have been used to compare the effects of the direct acting mutagens, methyl methanesulfonate (MMS) and N-nitroso- N-methylurea (NMU), and the indirect acting mutagens, benzo[a]pyrene (BAP), cyclophosphamide (CP), 9,10-dimethyl-1,2-benzanthracene (DMBA), and mitomycin C (MMC) in an inbred house mouse ( Mus domesticus) strain. The alkaline SCG assay was able to detect DNA damage from direct acting mutagens. However, it appears that, even at the highest concentrations tested, the SCG assay was not able to detect DNA damage caused by 3 of 4 indirect acting mutagens tested. The exception was BAP. The pbMN assay was sensitive to DNA damage caused by both groups of mutagens. Multiple injections did not increase the sensitivity of the SCG assay to the indirect acting mutagen CP. Further, simultaneous injections of CP and MMS, in one experiment, resulted in significantly lower ( p<0.05) average DNA ratios and micronucleated polychromatic erythrocyte counts than those obtained after treatment with MMS alone. Although the SCG assay has been shown to be sufficiently sensitive to detect DNA damage caused by both direct and indirect acting mutagens in deermice ( Peromyscus maniculatus) and bullheads ( Ameiurus nebulosus), similar results are not seen in the inbred house mouse strain tested.