Sodium metavanadate exhibits carcinogenic tendencies in vitro in immortalized human bronchial epithelial cells

Abstract

Pentavalent vanadium compounds induce intracellular changes in vitro that are consistent with those of other carcinogenic substances. While there is no clear evidence that vanadium compounds cause cancer in humans, vanadium pentoxide causes lung cancer in rodents after long-term inhalation exposures and in turn IARC has categorized it as a group 2B possible human carcinogen. The goal of this study was to investigate the carcinogenicity of NaVO3 in the human immortalized bronchial epithelial cell line, Beas-2B. Cells were treated with 10 μM NaVO3 for 5 weeks, with or without recovery time, followed by gene expression microarray analysis. In a separate experiment, cells were exposed to 1–10 μM NaVO3 for 4 weeks and then grown in soft agar to test for anchorage-independent growth. A dose-dependent increase in the number of colonies was observed. In scratch tests, NaVO3-transformed clones could repair a wound faster than controls. In a gene expression microarray analysis of soft agar clones there were 2010 differentially expressed genes (DEG) (adjusted p-value ≤ 0.05) in NaVO3-transformed clones relative to control clones. DEG from this experiment were compared with the DEG of 5 week NaVO3 exposure with or without recovery, all with adjusted p-values < 0.05, and 469 genes were altered in the same direction for transformed clones, 5 week NaVO3-treated cells, and the recovered cells. The data from this study imply that chronic exposure to NaVO3 causes changes that are consistent with cellular transformation including anchorage-independent growth, enhanced migration ability, and gene expression changes that were likely epigenetically inherited.

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

“…To test the possibility, we used Northern blotting to measure the percentage of polyadenylated H3.1 mRNA in total H3.1 mRNA before and after arsenic exposure. BEAS-2B cells were utilized because of the known association of arsenic exposure and lung cancer (44) as well as the ability of this cell line to undergo malignant transformation after metal exposure (21,22,27,45). Poly(A) ϩ mRNAs were purified from total RNA using poly(dT) beads, and the unbound fraction was designated as the poly(A) Ϫ fraction.…”

Malignant human cell transformation of Marcellus Shale gas drilling flow back water

“…BEAS-2B (ATCC, Manassas, VA) cells were cultured as previously described (Sun et al, 2011; Passantino et al, 2013) at 37°C in a humid 5% CO 2 atmosphere. BEAS-2B cells were seeded at 3×10 5 into 25 cm 2 polystyrene tissue culture flasks.…”

“…Colony formation and soft agar assay were then conducted, cells exhibited anchorage free growth were collected for wound healing assay according to previously published procedure (Passantino et al , 2013), for detailed information, please see supplemental materials.…”

“…In this study we employed BEAS-2B as well established models (Lee et al , 1993; Chen et al , 2006; Sun et al , 2011; Passantino et al , 2013) to investigate the malignant cell transformation of Marcellus shale gas drilling flow back water.…”

Tungsten exposure causes a selective loss of histone demethylase protein

“…Therefore, it is likely that other metal carcinogens may also alter the epigenetic program of cells, which may drive carcinogenesis. Recently, we have reported that the oxyanion vanadate may have tumorigenic potential based on its ability to induce transformation of BEAS‐2B cells in tissue culture . This research may have generated other studies investigating vanadium's ability to induce cancer .…”