The adaptive response in the scid mouse model: Is DNA-PKCS required?

We examined the role of DNA-PKcs in the adaptive response using the severe combined immunodeficient (SCID) mouse model that lacks functionally active DNA-PKcs molecules. We used DNA repair as measured by single cell gel elect rophoresis (Comet Assay) and apoptosis as endpoints to evaluate the adaptiv e response in two SCID cell lines. Additionally, we have examined the expre ssion of the base excision repair (BER) enzyme AP endonuclease (APE) and th e expression of NER related proteins p21, GADD45 and ERCC3 in an attempt to identify the induction of BER or NER pathways in adapted and non-adapted c ells. Our data suggests that the adaptive response is present in SCID cells , implying that DNA-PKcs is not required for the adaptive response. In SCID as well as in normal fibroblasts, the expression of APE was markedly incre ased and prolonged in the adapted cells. This suggests that low priming dos es of ionizing radiation may accentuate the BER pathway induced by the subs equent high dose and confer a survival advantage measured by lower percenta ges of apoptosis and more efficient repair of DNA damage. The presence of t he adaptive response in radiation-sensitive SCID cells known to be defectiv e in double strand break repair and nucleotide excision repair may be relat ed to an intact and inducible base excision repair mechanism.