Increased level of oxidative stress in genomically unstable cell clones.
Recently, we reported that ultraviolet radiation induces delayed mutations in mammalian cells. At the same level of cell death the oxidative component of sunlight (ultraviolet A radiation) was as potent in inducing this kind of genomic instability as ultraviolet B radiation. Ultraviolet B radiation predominantly harms cells by direct damage to DNA and thus is much more mutagenic than ultraviolet A radiation. From that study, clones with a significantly increased mutation rate in the hypoxanthine phosphoribosyl transferase gene were obtained. These genomically unstable clones were also found to have a higher variance in the number of chromosomes than the unirradiated control cells, indicating chromosomal instability. The mechanisms for induction and maintenance of radiation induced genomic instability are not known, but some studies suggest that reactive oxygen species might be involved. In the present study, we have measured the level of potentially mutagenic peroxides in the genomically unstable clones. The levels of intracellular peroxides and lipid peroxides were measured using the probes dihydrorhodamine 123 and diphenyl-1-pyrenyl-phosphine, respectively. The unstable clones had elevated levels of oxidants, supporting the hypothesis that intermediate reactive oxygen species might have a role in the maintenance of genomic instability induced by ultraviolet radiation.
Dahle
Jostein
J
Department of Biophysics, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. jostein.dahle@labmed.uio.no
Kvam
Egil
E
D000818:Animals; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism*; D006224:Cricetinae; D042822:Genomic Instability; D008054:Lipid Peroxides / Q000378:metabolism; D018384:Oxidative Stress; D013050:Spectrometry, Fluorescence
D008054:Lipid Peroxides