Effect of radioprotectors on DNA replication and mutation in mammalian cells after insult with ultraviolet radiation

Includes bibliographical references (pages [101]-117)For years, protection against the deleterious effects of ionizing radiation (e.g. x-rays) has been observed both at a cellular and at an organismal level by using chemicals called radioprotectors. However, the documentation for a similar protective effect of such compounds after exposure to non-ionizing radiation (e.g. ultraviolet [UV] radiation) is not nearly as extensive. The purpose of this study is to answer the question of whether or not these chemicals, specifically cysteamine and WR1065, confer protection against non-ionizing radiation damage, given the fact that they do protect against ionizing radiation damage. The principal mode of action of radioprotectors is thought to be free radical scavenging. Since present knowledge of non-ionizing radiation damage does not support free radical production, it is plausible to hypothesize that radioprotectors will not confer protection against non-ionizing radiation. In this study, Chinese hamster ovary (CHO) cells which are either repair-proficient ("AA8" cells) or repair-defective ("UV5" cells) were used. The effects of UV radiation (254nm wavelength) were measured in terras of cytotoxicity, mutagenesis and DNA synthesis in the presence or absence of either cysteamine or WR1065 (final concentration: 4mM). The drug was administered prior to irradiation and allowed to remain during irradiation, for a total drug exposure of 30 min. The cytotoxicity data obtained were conflicting. This was partly due to problems with the methodology used. The mutagenesis data obtained showed a trend towards a reduction in mutation frequency in UV5 cells after UV exposure in the presence of WR1065. The data on the rate of DNA synthesis after UV exposure showed no significant difference in thymidine incorporation in the presence or absence of either drug for up to 12 hours. This was true for both cell lines used. However, when the drugs were given alone, a consistent inhibition of DNA synthesis was observed for up to 12 hours. This correlates well with data obtained by others.M.S. (Master of Science