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

Southwest Environmental Science Center and Department of Pediatrics, University of Arizona College of Medicine, Tucson, USA

Cynthia D Fastje

Southwest Environmental Science Center and Department of Pediatrics, University of Arizona College of Medicine, Tucson, USA

Simon S Wong

Southwest Environmental Science Center and Department of Pediatrics, University of Arizona College of Medicine, Tucson, USA

Paul R Sheppard

Tree Ring Laboratory, University of Arizona College of Medicine, Tucson, USA

Stephanie J Macdonald

Southwest Environmental Science Center and Department of Pediatrics, University of Arizona College of Medicine, Tucson, USA

Gary Ridenour

Tree Ring Laboratory, University of Arizona College of Medicine, Tucson, USA

Juanita D Hyde

Southwest Environmental Science Center and Department of Pediatrics, University of Arizona College of Medicine, Tucson, USA

Mark L Witten

Southwest Environmental Science Center and Department of Pediatrics, University of Arizona College of Medicine, Tucson, USA, mwitten{at}peds.arizona.edu

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 mg/mL concentration, as measured by trypan-blue. Sierra Vista ore significantly increased cell growth with 0.15 and 1.5 mg/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 mg/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.

Key Words: gene microarray • leukemia • metallothionein • metals • transcriptomes • tungsten

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