15] Ultraviolet A- and singlet oxygen-induced mutation spectra

Abstract

Publisher Summary Genetic stability is an important prerequisite for the maintenance of the integrity and functions of each cell. Several environmental agents, as well as endogenous sources, are known to play a significant role in the formation of DNA lesions. Most of these lesions are repaired, but a few may escape and can lead to mutagenesis during trans -lesion replication or to chromosomal aberrations, and, finally, to tumorigenesis or cell death. The causal relationship between solar ultraviolet (UV) radiation and carcinogenesis has been well established. UVB radiation (290-320 nm) causes the direct formation of DNA photoproducts and gives rise to mutations in proto-oncogenes and tumor suppressor genes that eventually lead to skin cancer. Genotoxicity of UVA radiation (320-400 nm), which represents more than 90% of the terrestrial UV solar energy, is most likely induced by indirect mechanisms. After UVA photon absorption by an unidentified endogenous photosensitizer, reactive oxygen species are generated that could react with DNA without further intermediates (type I photosensitized reaction) or via singlet oxygen (type II photosensitized reaction). The singlet oxygen appears to be an early intermediate of UVA cellular response, judging by its involvement in signal transduction and gene induction. It belongs to reactive oxygen species (ROS) that are ubiquitous oxidizing agents generated in all aerobic organisms, endogenously as byproducts of respiration and inflammatory response and also exogenously after exposure to a variety of agents. This chapter discusses data on DNA lesions, DNA repair, and mutation spectra, which characterize the genotoxic potential of both singlet oxygen and UVA radiation, essentially in mammalian species.