Characterization of quinone reductase, glutathione and glutathione s-transferase in human myeloid cell lines: Induction by 1,2-dithiole-3-thione and effects on hydroquinone- induced cytotoxicity

Yunbo Li, Amalia Lafuente, Michael A. Trush

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we have characterized quinone reductase (QR), glutathione (GSH), glutathione S-transferase (GST) and their induction by a chemoprotector, 1,2-dithiole-3-thione (D3T), in the human myeloid cell lines ML-1 and HL-60. In addition, we also examined the toxicity of hydroquinone (HQ), a benzene metabolite, to these two cell lines. Both of the cell lines contain a basal level of cellular GSH, which is similar in the two cell lines. Although ML-1 cells contain much higher QR specific activity than HL-60 cells, which are relatively QR deficient, the GST specific activity of ML-1 cells is 1.8 times less than that of HL-60 cells. Immunoblot experiments showed that the GST in these two cell lines is GST π. In addition, HL-60 cells exhibit 4.5 times more myeloperoxidase specific activity than ML-1 cells. Inclusion of D3T in the cultures could induce significant increase in cellular GSH content and QR activity, but not GST activity in either cell line. Treatment with HQ caused both inhibition of cell proliferation and loss of cell viability in these two myeloid cell lines. HQ treatment also resulted in a significant depletion of cellular GSH, which preceded the loss of cell viability. Pretreatment of Both cell lines with buthionine sulfoximine, an inhibitor of GSH biosynthesis, markedly increased HQ-induced toxicity. In contrast, the presence of dicumarol, a QR inhibitor, failed to potentiate HQ-induced toxicity in ML-1 cells. On the other hand, pretreatment of these two myeloid cell lines with D3T significantly protected against HQ-induced inhibition of cell proliferation and cell death. Therefore, the above results suggest that GSH but not QR is an important factor involved in the toxicodynamics of HQ in these myeloid cells.

Original languageEnglish (US)
Pages (from-to)901-916
Number of pages16
JournalLife Sciences
Volume54
Issue number13
DOIs
StatePublished - 1994

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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