Hyperoxia and gamma-irradiation were found to be mutagenic in a transformed Syrian hamster cell line in a dose-dependent manner. The frequency of resistance to
6-thioguanine increased from 10 per 10(6) survivors after 48 h of growth in 70% O2 to 32.6 (highly significant) after 75 h. Increasing the
oxygen tension to 95% resulted in a significant mutagenic response in only 44 h. At equitoxic doses, gamma-irradiation was 4 times more mutagenic than 70% O2. After growth in
hyperoxia, the cells showed an enhancement of
catalase activity,
glutathione peroxidase activity and
glutathione levels but there was little effect on
superoxide dismutase activity.
Diethyldithiocarbamate (3 mM, 1.5 h) was mutagenic in normoxia and potentiated the mutagenic activity of both gamma-irradiation and
hyperoxia. Cells thus treated showed an 855 reduction in
superoxide dismutase activity. When
diethyldithiocarbamate was used in conjunction with a direct-acting
alkylating agent, the mutagenic response was only additive. Depletion of cellular
glutathione with
buthionine sulfoximine (0.2 mM) or inhibition of
catalase activity with
aminotriazole (100 mM) was also effective in potentiating the mutagenic response of gamma-irradiation and
hyperoxia. The data demonstrates that endogenously produced activated
oxygen species are mutagenic to hamster cells in culture and suggest that aerobic organisms are subject to an unavoidable background risk due to living in an
oxygen atmosphere.