Bluegill sunfish BF-2 fibroblasts were used to evaluate the in vitro cytotoxicities of 1,4-naphthoquinone (NQ), 5,8-dihydroxy-1,4-NQ, and 2,3-dichloro-1,4-NQ (dichlone); comparisons were made with previously obtained data on the response of human hepatoma HepG2 cells. For both cell types, the sequence of potency was 5,8-dihydroxy-1,4-NQ>1,4-NQ>dichlone. Dichlone, and, although to a lesser extent, 1,4-NQ and 5,8-dihydroxy-1-4-NQ, induced endoreduplication in the BF-2 cells; for the HepG2 cells, endoreduplication was induced only with dichlone. Exposures to the three NQs reduced intracellular glutathione levels in both cell types. For the BF-2 and HepG2 cells, pretreatments with buthionine sulfoximine (BSO), a glutathione-depleting agent, potentiated the cytotoxicity of 5,8-hydroxy-1,4-NQ and dichlone; pretreatment with dicoumarol, an inhibitor of DT-diaphorase, had no effect on toxicity of these two NQs. Apparently, for these two quinones the predominant metabolic pathway in both the BF-2 and HepG2 cells involved redox cycling via a one-electron reduction reaction, generating reactive oxygen intermediates that consumed intracellular glutathione. Pretreatment of the BF-2 cells with BSO, but not with dicoumarol, potentiated the toxicity of 1,4-NQ, again indicating that metabolism occurred via one electron reduction. However, for the HepG2 cells, pretreatment with dicoumarol, but not with BSO, potentiated the cytotoxicity of 1,4-NQ. Apparently, in the HepG2, as compared to the BF-2, cells, 1,4-NQ was metabolized by DT-diaphorase in a reaction involving a two electron reduction.
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Babich, H., Palace, M.R., Borenfreund, E. et al. Naphthoquinone cytotoxicity to bluegill sunfish BF-2 cells. Arch. Environ. Contam. Toxicol. 27, 8–13 (1994). https://doi.org/10.1007/BF00203880
- HepG2 Cell
- Reactive Oxygen Intermediate
- Intracellular Glutathione