Adipose tissue stem cell-derived hepatic progenies as an in vitro model for genotoxicity testing.

Adipose tissue stem cell-derived hepatic progenies as an in vitro model for genotoxicity testing. Arch Toxicol. 2018 Mar 16;: Authors: Tomc J, Kološa K, Žegura B, Kamenšek U, Breznik B, Turnšek TL, Filipič M Abstract The problem of the currently used routine genotoxicity tests is relatively low predictivity of in vitro tests for in vivo genotoxicity and carcinogenicity. An important reason is considered to be inadequate expression of xenobiotic-metabolizing enzymes in indicator cell lines. The aim of our study was to generate metabolically active differentiated hepatic progenies (hDHP) from human adipose tissue-derived mesenchymal stem cells (hASC) for genotoxicity testing. hDHP, generated using a three-step hepatic differentiation procedure, expressed hepatic properties such as glycogen storage and albumin secretion. The results of the comet assay demonstrated comparable sensitivity of hASC and hDHP to detect DNA damage induced by a direct acting genotoxic agent tert-butylhydroperoxide. Exposure to model indirect acting genotoxins benzo(a)pyrene, aflatoxin B1, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine did not induce DNA damage in hASC, while hDHP cells detected DNA damage induced by benzo(a)pyrene and aflatoxin B1, indicating their metabolic activity. The gene and protein expression analysis confirmed the presence of key enzymes involved in metabolism of the three genotoxins in hDHP cells. Moreover, the exposure of hD...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research