Dose-dependent transcriptome changes by metal ores on a human acute lymphoblastic leukemia cell line

Toxicol Ind Health. 2003 Oct;19(7-10):157-63. doi: 10.1191/0748233703th185oa.

Abstract

The increased morbidity of childhood leukemia in Fallon, Nevada and Sierra Vista, Arizona has prompted great health concern. The main characteristic that these two towns share is the environmental pollution attributed to metal ore from abandoned mining operations. Consequently, we have investigated the transcriptome effects of metal ores from these endemic areas using a human T-cell acute lymphoblastic leukemia cell line (T-ALL). Metal ore from Fallon significantly increased cell growth after 24, 48 and 72 h of incubation at 1.5 microg/mL concentration, as measured by trypan-blue. Sierra Vista ore significantly increased cell growth with 0.15 and 1.5 microg/mL following 72 h of incubation. From human cDNA microarray, results indicate that in total, eight genes, mostly metallothionein (MT) genes, were up-regulated and 10 genes were down-regulated following treatment of the T-ALL cells with 0.15 and 1.5 microg/mL of metal ores at 72 h, in comparison with untreated cells. Twenty-eight metals of both ores were quantified and their presence may be associated with the cell growth rate and dose-dependent activation of transcriptomes in immature T-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arizona
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Environmental Pollution / adverse effects*
  • Gene Expression / drug effects
  • Humans
  • In Vitro Techniques
  • Metallothionein / drug effects*
  • Metallothionein / genetics
  • Metals, Heavy / toxicity*
  • Mining
  • Nevada
  • Oligonucleotide Array Sequence Analysis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / chemically induced
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • RNA / isolation & purification
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Tungsten / toxicity
  • Up-Regulation / drug effects

Substances

  • Metals, Heavy
  • RNA
  • Metallothionein
  • Tungsten