TRANSCRIPTION AND ACTIVITY OF ANTIOXIDANT ENZYMES AFTER IONIZING IRRADIATION IN RADIATION-RESISTANT AND RADIATION-SENSITIVE

The involvement of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in radiobiological process es has been described at the enzyme activity level. We irradiated radi ation-resistant (RR) and radiation-sensitive (RS) mice and studied ant ioxidant enzymes at the transcriptional and activity level. In additio n, aromatic hydroxylation and lipid peroxidation parameters were deter mined to study radiation resistance at the oxidation level. RS BALB/c/ J Him mice and RR C3H He/Him mice were whole-body-irradiated with x-ra ys at 2, 4, and 6 Gy and killed 5, 15, and 30 min after irradiation. m RNA was isolated from liver and hybridized with probes for antioxidant enzymes and beta-actin as a housekeeping gene control. Antioxidant en zyme activities were determined by standard assays. Parameters for aro matic hydroxylation (o-tyrosine) and lipid peroxidation (malondialdehy de) were determined by HPLC methods. Antioxidant transcription was unc hanged in contrast to antioxidant activities; SOD and CAT activities w ere elevated within 15 min in RR animals but not in RS mice, at all do ses studied. Glutathione peroxidase activity was not different between RR and RS mice and was only moderately elevated after irradiation. No significant differences were found between RR and RS animals at the o xidation level, although a radiation dose-dependent increase of oxidat ion products was detected in both groups. We found that ionizing irrad iation led to increased antioxidant activity only minutes after irradi ation in the absence of increased transcription of these antioxidant e nzymes. RR animals show higher antioxidant enzyme activities than do R S mice, but oxidation products are comparable in RS and RR mice. As un changed transcription of antioxidant enzymes could not have been respo nsible for the increased antioxidant enzyme activities, preformed anti oxidant enzymes should have been released by the irradiation process. This would be in agreement with previous studies of preformed, stored SOD. The finding of higher SOD and CAT activities in RR than in RS ani mals could point to a role for these antioxidant enzymes for the proce ss of radiation sensitivity.