SINGLET OXYGEN - A PRIMARY EFFECTOR IN THE ULTRAVIOLET-A NEAR-VISIBLELIGHT INDUCTION OF THE HUMAN HEME OXYGENASE GENE/

Both singlet oxygen and the hydroxyl radical are generated in mammalia n cells by UVA (320-380 nm) and possibly near-visible (380-420 nm) rad iation. We have modulated the cellular levels of these two reactive ox ygen species in order to compare their involvement in the induction of the human heme oxygenase (HO) gene by broad spectrum UVA/near-visible light (UVA/NVL). Irradiation in deuterium oxide (in which singlet oxy gen has a longer half-life) enhances the broad spectrum UVA/NVL induct ion of this gene. Sodium azide and L-histidine which are scavengers of both singlet oxygen and the hydroxyl radical reduce the fluence-depen dent accumulation of HO mRNA, while compounds which are only hydroxyl radical scavengers, namely, mannitol and dimethyl sulfoxide do not. Ro se Bengal, a known generator of singlet oxygen, also increases the HO mRNA levels, and this induction is enhanced in deuterium oxide. We con clude that the observed effects of deuterium oxide and singlet oxygen scavengers on HO mRNA levels are not due to a nonspecific effect on tr anscription but that singlet oxygen is a primary effector in the UVA/N VL induction of the human heme oxygenase gene.