SYNERGISTIC TOXICITY OF DEPLETED URANIUM AND UVB LIGHT IN CHINESE HAMSTER OVARY CELLS

Filbert Yazzie , Diane M. Stearns, PhD

SYNERGISTIC TOXICITY OF DEPLETED URANIUM AND UVB LIGHT IN CHINESE HAMSTER OVARY CELLS

Questions regarding the toxicity of uranium have largely focused on its radiological modes of action, ignoring its chemical reactivity.  One unexplored pathway for the chemical toxicity of uranium involves the photoactivation of uranyl ion by UV light to produce U5+ and a uranium-bound oxygen radical.  We are testing the hypothesis that co-exposure of DNA to uranium and UVB irradiation should produce different types of DNA damage relative to individual exposures, namely oxygen radical-induced strand breaks for combined exposures vs. adduct-type lesions for uranium exposure, cyclopyrimidine dimers after UVB light exposure.  We are testing this hypothesis in a series of Chinese hamster ovary cell lines that are deficient in different steps of DNA repair.  The CHO EM9 line, which is XRCC1 deficient, is more sensitive to DNA strand breaks than the repair proficient parental CHO AA8 line, and the CHO UV5 line, which is ERCC2 deficient, is more sensitive to UV photoproducts and bulky adducts than the CHO AA8 line.  We propose that co-exposures to depleted uranium as uranyl acetate and UVB light at 302 nm will result in more cell death than individual exposures in all three lines, and that comparative treatments will be more cytotoxic in the repair deficient lines than the parental line.  Preliminary results support our hypothesis in that increased cytotoxicity was observed when exposures to uranium and UVB and were combined.  Furthermore, both individual and combined exposures were more cytotoxic in repair deficient CHO EM9 cells than parental CHO AA8 cells.  Implications for this work may extend to the inclusion of skin as a target organ for uranium toxicity, especially in populations with high uranium and solar radiation exposures.  This work was supported by NIH grants ES019703 and U54CA143925.  Mr. Yazzie was supported by the Initiative Maximizing Student Diversity (MSD/IMSD) Program, NIH GM056931.

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