Psoralen and near ultraviolet light; a probe for study of control of protein synthesis

Abstract

THE study of the control of protein synthesis in eukariotic cells usually involves the use of chemical inhibitors of macromolecule synthesis¹. The drawback of these procedures is that the inhibitors have side effects which do not allow conclusive interpretations. Furthermore, the precise timing of the inhibitor effect is not always possible due to the lack of knowledge of the effective in vivo concentration and the rate of its entry into the cells. Furocoumarins (psoralens) photosensitise biological systems to near ultraviolet (NUV) light (300–400 nm) (refs 2–4). Psoralen and its derivatives react with pyrimidine bases in DNA when irradiated with NUV light to form monoadducts and DNA crosslinks^5,6, the latter being the main lesion responsible for the biological damage in bacteria and mammalian cells^4,7. Since the photoreactions in the cells are specifically with DNA^8,9 and lead to its immediate inactivation as a template for DNA and RNA synthesis⁹, we have considered the use of this system for the study of control of protein synthesis. The degree of inactivation of DNA can be easily controlled by varying the NUV light dose, thus avoiding the complications involved in the use of drugs.