This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Varnes, M. E. Articles by Biaglow, J. E. Search for Related Content PubMed PubMed Citation Articles by Varnes, M. E. Articles by Biaglow, J. E.

Interactions of the Carcinogen 4-Nitroquinoline 1-oxide with the Non-Protein Thiols of Mammalian Cells¹

Division of Radiation Biology, Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106

The carcinogen 4-nitroquinoline 1-oxide (4-NQO) was found to rapidly deplete non-protein thiols (NPSH) from Ehrlich ascites tumor cells and V79 Chinese hamster fibroblasts. The effects of NPSH on 4-NQO metabolism were studied by measuring 4-hydroxyaminoquinoline 1-oxide formation, CN^–1-insensitive oxygen consumption, and reduction of ferricytochromes c + c₁ in normal cells and in cells pretreated with the thiol reagent N-ethylmaleimide. Removal of thiols before treatment with 4-NQO resulted in increased production of 4-hydroxyaminoquinoline 1-oxide and increased production of nitro radicals. The NPSH thus appeared to play a significant role in 4-NQO detoxification. Glutathione, when present in culture medium during 4-NQO treatment, protected V79 cells from 4-NQO toxicity. Several mechanisms for reaction of 4-NQO with intracellular NPSH were indicated. Both V79 and Ehrlich cells contained appreciable amounts of glutathione S-transferase (EC 2.5.1.18), which catalyzes the nucleophilic substitution of the nitro group of 4-NQO with thiols. Greater thiol loss under oxic than under hypoxic conditions suggested oxidation by superoxide, peroxide, or hydroxyl radical formed in the course of 4-NQO reduction. In addition, reaction of thiols with nitro radicals or with nitrosoquinoline 1-oxide was indicated by the inhibitory effect of glutathione on oxygen consumption in solutions of 4-NQO and sodium ascorbate.

¹ This investigation was supported in part by Grants CA 13747, CA 19283, and CA 15901 awarded by the National Cancer Institute, NIH.

² To whom requests for reprints should be addressed.

Received 10/19/78. Accepted 4/17/79.

This article has been cited by other articles:

				H. Inano, M. Onoda, N. Inafuku, M. Kubota, Y. Kamada, T. Osawa, H. Kobayashi, and K. Wakabayashi Potent preventive action of curcumin on radiation-induced initiation of mammary tumorigenesis in rats Carcinogenesis, October 1, 2000; 21(10): 1835 - 1841. [Abstract] [Full Text] [PDF]

				B. Teicher, T. Herman, S. Holden, Y. Wang, M. Pfeffer, J. Crawford, and E Frei 3rd Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo Science, March 23, 1990; 247(4949): 1457 - 1461. [Abstract] [PDF]

				P. Cerutti Prooxidant states and tumor promotion Science, January 25, 1985; 227(4685): 375 - 381. [Abstract] [PDF]