[Molecular mechanism involved in chromium(VI) toxicity].
Chromium exists in many different oxidation states in the environment, Cr(VI) and Cr(III) being the most stable forms. Chromium has been known for over 100 years to be a human carcinogen. The greatest risk of cancer from chromium exposure is associated with Cr(VI). Cr(VI) enters cells via the sulfate anion transporter system and is reduced to intermediate oxidation states, such as Cr(V) and Cr(IV), in the process of forming stable Cr(III) forms. It is known that Cr(VI) affects expression of various genes. Metal responsive element-binding transcription factor-1 (MTF-1) is involved in sensing heavy metal load and the induced transcription of several protective genes, including metallothionein (MT)-I, MT-II, zinc transporter-1, and gamma-glutamylcysteine synthetase. Cr(VI) inhibits zinc-induced MT transcription via modifying transactivation potential of MTF-1. However, the molecular mechanism for the Cr(VI)-mediated inhibition of MTF-1 has not been fully elucidated. In this review, I briefly summarize the previous studies and discuss the current status of research on Cr(VI) toxicity and Cr(VI)-mediated inhibition against transcription.
Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata City 573-0101, Japan. tomoki@setsunan.ac.jp
Tomoki
T
Kimura
D002352:Carrier Proteins / Q000235:genetics; D002412:Cations; D002857:Chromium / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D006655:Histone Deacetylases; D008668:Metallothionein / Q000235:genetics; D016296:Mutagenesis / Q000187:drug effects; D016328:NF-kappa B; D009369:Neoplasms / Q000209:etiology; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D050880:p300-CBP Transcription Factors; D000097809:Transcription Factor MTF-1
D002352:Carrier Proteins; D002412:Cations; D002857:Chromium; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D008668:Metallothionein; D016328:NF-kappa B; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000097809:Transcription Factor MTF-1; C017800:zinc-binding protein