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[Cancer Research 53, 4505-4510, October 1, 1993]
© 1993 American Association for Cancer Research

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Singlet Oxygen: A Primary Effector in the Ultraviolet A/Near-Visible Light Induction of the Human Heme Oxygenase Gene1

Sharmila Basu-Modak and Rex M. Tyrrell2

Swiss Institute for Experimental Cancer Research, Physical Carcinogenesis Unit, CH-1066 Epalinges/Lausanne, Switzerland

2 To whom reprint requests should be addressed, at Ch. des Boveresses 155, Ch-1066 Epalinges, Switzerland.

Both singlet oxygen and the hydroxyl radical are generated in mammalian cells by UVA (320-380 nm) and possibly near-visible (380-420 nm) radiation. We have modulated the cellular levels of these two reactive oxygen 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 oxygen has a longer half-life) enhances the broad spectrum UVA/NVL induction of this gene. Sodium azide and L-histidine which are scavengers of both singlet oxygen and the hydroxyl radical reduce the fluence-dependent accumulation of HO mRNA, while compounds which are only hydroxyl radical scavengers, namely, mannitol and dimethyl sulfoxide do not. Rose Bengal, a known generator of singlet oxygen, also increases the HO mRNA levels, and this induction is enhanced in deuterium oxide. We conclude that the observed effects of deuterium oxide and singlet oxygen scavengers on HO mRNA levels are not due to a nonspecific effect on transcription but that singlet oxygen is a primary effector in the UVA/NVL induction of the human heme oxygenase gene.

1 This work was supported by grants from the Swiss League against Cancer and the Swiss National Science Foundation (31.30880.91).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 11/ 4/92. Accepted 7/28/93.




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Copyright © 1993 by the American Association for Cancer Research.