Normal G(0) pig lymphocytes were maintained in a hypoxic or aerobic environment for one hour and then concurrently exposed to bleomycin at varying concentrations for a second hour. The cytochalasin-block micronucleus assay was used to determine cytotoxicity. Exposure to transient hypoxia significantly decreased the frequency of bleomycin-induced micronuclei per cell as compared to that observed in oxygenated cells. Furthermore, the frequency of micronuclei per hypoxic cell did not correspond to any increase in bleomycin dose as observed in oxygenated cells. These data demonstrate the significance of transient hypoxia in the resistance of G(0) cells to the cytotoxic effects of bleomycin and may explain the observed selectivity of tumor tissue response to bleomycin.

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