Analysis of oxidative DNA damage and HPRT mutations in humans after hyperbaric oxygen treatment.
DNA damage induced by reactive oxygen species (ROS) seems to play an important role in the induction of mutations and cancer. We have recently shown that hyperbaric oxygen (HBO) treatment of volunteers (i.e., exposure to 100% oxygen at a pressure of 2.5 ATA) induces DNA damage detected in leukocytes with the comet assay. Using formamidopyrimidine-DNA glycosylase (FPG protein) we provided indirect evidence for the induction of oxidative DNA base damage. We now comparatively evaluated FPG-sensitive sites with the comet assay and 7,8-dihydro-8-oxo-deoxyguanosine (8-OHdG) with HPLC analysis after a single HBO. As 8-OHguanine (8-OHgua) is one of the major DNA modifications induced by ROS and a pre-mutagenic lesion, we looked for HBO-induced mutations at the HPRT locus with the T cell cloning test. We also determined the genotypes for glutathione transferases (GST) and tested a possible influence of the GSTM1 and GSTT1 genotypes on the sensitivity of subjects against HBO-induced genotoxicity. Our results indicate that despite a clear induction of FPG-sensitive sites no increased levels of 8-OHdG and no induction of HPRT mutations was detected in lymphocytes after HBO. Furthermore, the DNA effects in the comet assay and the mutant frequencies in the HPRT test seem to be unrelated to the GST genotypes of the test subjects.
Dennog
C
C
Universitätsklinikum Ulm, Abteilung Medizinische Genetik, Germany.
Gedik
C
C
Wood
S
S
Speit
G
G
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008297:Male; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D018384:Oxidative Stress
D000080242:8-Hydroxy-2'-Deoxyguanosine; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine; D005982:Glutathione Transferase; D007041:Hypoxanthine Phosphoribosyltransferase; D009699:N-Glycosyl Hydrolases; C413545:glutathione S-transferase T1