Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer

Abstract

The complex process of carcinogenesis begins with transformation of a single cell to favor aberrant traits such as loss of contact inhibition and unregulated proliferation – features found in every cancer. Despite cancer’s widespread prevalence, the early events that initiate cancer remain elusive, and without knowledge of these events cancer prevention is difficult. Here we show that exposure to As, Cr, Ni, or Vanadium (V) promotes changes in gene expression that occur in conjunction with aberrant growth. We exposed immortalized human bronchial epithelial cells to one of four metals/metalloid for four to eight weeks and selected transformed clonal populations based upon anchorage independent growth of single cells in soft agar. We detected a metal-specific footprint of cancer-related gene expression that was consistent across multiple transformed clones. These gene expression changes persisted in the absence of the progenitor metal for numerous cell divisions. Our results show that even a brief exposure to a carcinogenic metal may cause many changes in gene expression in the exposed cells, and that from these many changes, the specific change(s) that each metal causes that initiate cancer likely arise.

Tungsten-induced carcinogenesis in human bronchial epithelial cells

“…Previously, arsenic, chromium, nickel and vanadium have been studied for their ability to induce transformation of Beas-2B cells [12, 35]. This study explores the carcinogenic potential of tungsten, a metal that has not been evaluated in metal-induced carcinogenesis investigations.…”

Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression

“…BL41 and PBMCs were plated at 5 ϫ 10 5 /ml in 10-cm 2 culture dishes; BEAS-2B and A549 cells were plated at 2.5 ϫ 10 5 /ml in 10-cm 2 culture dishes. For arsenic exposure, cells were treated with sodium meta-arsenite (NaAsO 2 ) with doses ranging from 0 to 1 M for 48 h. BEAS-2B, arsenic-transformed BEAS-2B, and Cr(VI)-transformed clones (26,27), respectively, were grown in DMEM containing 10% FBS and 1% penicillinstreptomycin. Transformation assays were conducted as described previously (28,29).…”

Long-term exposures to low doses of cobalt nanoparticles induce cell transformation enhanced by oxidative damage

“…Thus, several in vitro cancer hallmarks were evident under our long-term study conditions such as morphological changes, secretion of MMPs or anchorage-independent cell growth. Firstly, we observed morphological changes in the exposed MEF cells, such as loss of cell shape and cell elongation, which are indicators of cancer-like phenotypic changes (Clancy et al, 2012). In addition, our results show evidence that there is increased secretion of MMPs considered as an early biomarker of the carcinogenic effects induced by toxicants.…”