Journal Article

Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer chemopreventive dithiolethiones

Thomas Primiano, Thomas W. Kensler, Periannan Kuppusamy, Jay L. Zweier and Thomas R. Sutter

in Carcinogenesis

Volume 17, issue 11, pages 2291-2296
Published in print November 1996 | ISSN: 0143-3334
Published online November 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.11.2291
Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer
                    chemopreventive dithiolethiones

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Treatment of rats with the cancer chemopreventive agent 1, 2-dithiole-3-thione (D3T) resulted in a significant increase in hepatic heme oxygenase (HO) activity, which corresponded to increased protein levels of HO-1. Upon further analysis of proteins related to heme metabolism, the level of ferritin, the major iron storage protein in liver, was also found to be elevated. Diminished levels of intracellular free iron were monitored by EPR spectroscopy at times after administration of D3T that suggested that increased ferritin content sequesters intracellular iron. The increased levels of protein were associated with increased levels of steadystate RNA of HO-1 and the light (FL) and heavy (FH) subunits of ferritin. A direct relationship between enhanced rates of gene transcription and elevated levels of HO-1 and ferritin RNA was found. The inductions of FL and FH, but not HO-1, were sensitive to cycloheximide, suggesting that in vivo these genes are regulated by distinct D3Tresponsive transcriptional mechanisms. The known protective roles for induced HO-1 and ferritin in cellular stress have been suggested to include increased levels of the antioxidant bilirubin and enhanced sequestration of intracellular iron into ferritin, which can effectively reduce iron-mediated reactive oxygen generation. Thus, protective actions of D3T against the cytotoxic and carcinogenic consequences of chemicals that exert electrophilic or oxidative stresses may be mediated, in part, by the induction of HO-1, FL and FH.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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