Relationship between base excision repair capacity and DNA alkylating agent sensitivity in mouse monocytes

Base excision repair (BER) capacity and the level of DNA polymerase (beta -pol) are higher in mouse monocyte cell extracts when cells are treated with oxidative stress-inducing agents. Consistent with this, such treated cells are more resistant to the cytotoxic effects of methyl methanesulfonate (MMS), which produces DNA damage considered to be repaired by the BER pathway. In contrast to the up-regulation of BER in oxidatively stressed cells, cells treated with the cytok-me interferon-gamma (IFN-gamma) are down-regulated in both BER capacity of the cell extract and level of beta -pol. We find that cells treated with IFN-gamma are more sensitive to MMS than untreated cells. These results demonstrate concordance between beta -pol level, BER capacity and cellular sensitivity to a DNA methylation-inducing agent. The results suggest that BER is a significant defense mechanism in mouse monocytes against the cytotoxic effects of methylated DNA. (C) 2001 Elsevier Science B.V. All rights reserved.