Oral exposure to BDE-209 modulates metastatic spread of melanoma in C57BL/6 mice inoculated with B16–F10 cells. (December 2020)

• Record Type: Journal Article
• Authors: Brito, Patricia Manuitt; Biscaia, Stellee Marcela Petris; de Souza, Tugstenio Lima; Ramos, Amandia Batscheuer; Leão-Buchir, Joelma; de Almeida Roque, Aliciane; de Lima Bellan, Daniel; da Silva Trindade, Edvaldo; Filipak Neto, Francisco; de Oliveira Ribeiro, Ciro Alberto
• Is Part Of: Chemosphere. Volume 260(2020)
• Publication Date: 2020-12
• Subjects: BDE-209 -- Metastases -- B16–F10 -- Hepatotoxicity -- Flame retardants; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2020.127556
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Polybrominated diphenyl ethers (PBDEs) are brominated, persistent and bioaccumulative flame retardants widely used in the manufacture of plastic products. Decabromodiphenyl ether (BDE-209) is the most prevalent PBDE in the atmosphere and found in human blood, breast milk and umbilical cord. In vitro studies showed that BDE-209 interferes with murine melanoma cells (B16F10), modulating cell death rates, proliferation and migration, important events for cancer progression. In order to evaluate if BDE-209 modulates metastasis formation in murine models, C57BL/6 mice were exposed to BDE-209 (0.08, 0.8 and 8 μg⁄kg) via gavage (5-day intervals for 45 days) (9 doses in total). Then, mice were inoculated with melanoma cells (B16–F10) at caudal vein receiving 4 additional doses of BDE-209. At 20th day post-cell inoculation, blood, lung, liver, kidney and brain were sampled for hematological, biochemical and morphological analyses. The slightly higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood and pro-oxidant state in the liver of BDE-exposed mice indicated liver damage. Although the in vivo approach is for metastasis formation in the lung, they were unexpectedly observed in non-target organs (liver, brain, kidney and gonads). The similarity test showed high proximity among individuals from the control and a dissimilarity index between the control and exposed groups. The present data corroborate the known hepatotoxicity of BDE-209 to mice (C57BL/6) and demonstrate for the first time the increase of metastatic dissemination of B16F10 cells in vivo due to previous and continuous BDE-209 exposure, revealing possible implications of this organic compound with melanoma malignancy related traits. Graphical abstract: Image 1 Highlights: BDE-209 increase the incidence of metastases in organs of mice. The occurrence of metastases in non-target organ was an unexpected finding. The exposure to BDE-209 favor the in vivo metastatic spread of melanoma. BDE-209 possibly is implicated with melanoma malignancy related traits.