DNA damage by drugs and radiation: what is important and how is it measured?

Abstract

DNA is the most important target for drug and radiation induced cell killing. The mode of cell killing by cytotoxic drugs and radiation has been derived by correlating the type and quantity of DNA damage induced with lethality. Cytotoxic drugs can be classified by their main mode of action, while ionising radiation causes a range of lesions with the DNA double-strand break (dsb) being the most significant. Strand-breaks are measured from the reduction in the size of DNA molecules following treatment. Molecule size can be derived from the rate that DNA fragments sediment when centrifuged, elute through filters or migrate under electrophoresis. The effect of strand-breaks on DNA loop supercoiling allow a sensitive assay of DNA damage. Specific assays for base damage and drug adducts include changes in chromatographic mobility or binding by specific antibodies. By comparing the levels of damage in the genome overall with damage in specific gene targets, regions susceptible to damage induction, and varying in repair efficiency, have been revealed.