Antibodies and DNA Photoproducts: Applications, Milestones and Reference Guide

Abstract

Polyclonal and monoclonal antibodies recognizing the primary DNA photoproducts induced by ultraviolet radiation (UVR) have proven to be essential tools in the study of photochemical and photobiological phenomena. As specific ''DNA damage binding proteins'' these reagents have been used to develop a diverse array of technical procedures applied to a plethora of important problems in DNA photochemistry and the biological effects of UVR at the molecular, developmental, organism and population levels. This survey attempts to cover this science from an historical perspective and to reveal the great breadth of discovery and contribution associated with the development and application of DNA damage antibodies to the current body of science.Three papers published in the 1960s were seminal to the development of immunoassays for the study of photochemical and photobiological phenomena. In 1960 Rosalyn Yalow and Solomon Berson published a paper in the Journal of Clinical Investigation entitled ''Immunoassay of endogenous plasma insulin in man'' (1), which described the development of a sensitive radioimmunoassay (RIA) to measure minute quantities of hormones in blood samples. This technique played a seminal role in the exponential expansion of research in medicine and the biological sciences over the past half century. In 1977 Dr. Yalow was awarded the Nobel Prize in Medicine for her work. In 1964 Otto Plescia and colleagues published a paper in the Proceedings of the National Academy of Sciences entitled ''Production of antibodies to denatured deoxyribonucleic acid (DNA)'' (2). Using a technique whereby singlestranded DNA was electrostatically coupled to methylated bovine serum albumin they were able to elicit an immune response in rabbits. In the wake of this paper it was not long before a group led by Lawrence Levine and Helen van Vanukis published an article in Science in 1966 entitled ''Antibodies to photoproducts of deoxyribonucleic acids irradiated with ultraviolet light'' (3). Using the technique established by Plescia, this group was able to produce a rabbit antiserum using DNA irradiated with 270 nm light with antigenic determinants that were reversible by 235 nm light and responsive to UV-irradiated thymidine nucleotides. It appeared that antibodies had been created in response to thymine dimers.Over the course of the following two decades a number of polyclonal and monoclonal antibodies to various UV-induced DNA lesions were produced and characterized. The technology that developed blossomed and has been applied to a broad spectrum of problems in photochemistry, the biological response to UV radiation (UVR), photomedicine and environmental photobiology. Early immunoassays generated DNA repair curves showing rapid removal of most antibody binding sites leaving behind a significant remnant (4,5). These results were not consistent with the known repair kinetics using biochemical and enzymatic techniques. Subsequently, it was discovered that polyclonal antisera raised against heavily UVirradiated DNA contai...