The repair of identified large DNA adducts induced by 4-nitroquinoline-1-oxide in normal or xeroderma pigmentosum group A human fibroblasts, and the role of DNA polymerases alpha or delta

Abstract

4-Nitroquinoline-1-oxide (4NQO) reacts with DNA primarily at the N2 and C8 of guanosine, with a small percent of reaction at the N6 of adenosine. In human cells it has been unclear whether or not all 4NQO-induced adducts are removed by a nucleotide excision repair mechanism. In this paper we demonstrate that the inhibitor of DNA polymerases alpha and delta, aphidicolin, blocks the repair of all 4NQO adducts. Hence excision repair must operate on all of these lesions. After 4NQO the residual excision repair seen in a xeroderma pigmentosum group A cell line virtually totally defective in UV repair was 40-60% of that in normal cells. Therefore there must be some differences between the excision repair operating on UV as opposed to 4NQO-induced DNA damage.