Major changes of cell function and toxicant sensitivity in cultured cells undergoing mild, quasi-natural genetic drift.

Major changes of cell function and toxicant sensitivity in cultured cells undergoing mild, quasi-natural genetic drift. Arch Toxicol. 2018 Oct 08;: Authors: Gutbier S, May P, Berthelot S, Krishna A, Trefzer T, Behbehani M, Efremova L, Delp J, Gstraunthaler G, Waldmann T, Leist M Abstract Genomic drift affects the functional properties of cell lines, and the reproducibility of data from in vitro studies. While chromosomal aberrations and mutations in single pivotal genes are well explored, little is known about effects of minor, possibly pleiotropic, genome changes. We addressed this question for the human dopaminergic neuronal precursor cell line LUHMES by comparing two subpopulations (SP) maintained either at the American-Type-Culture-Collection (ATCC) or by the original provider (UKN). Drastic differences in susceptibility towards the specific dopaminergic toxicant 1-methyl-4-phenylpyridinium (MPP+) were observed. Whole-genome sequencing was performed to identify underlying genetic differences. While both SP had normal chromosome structures, they displayed about 70 differences on the level of amino acid changing events. Some of these differences were confirmed biochemically, but none offered a direct explanation for the altered toxicant sensitivity pattern. As second approach, markers known to be relevant for the intended use of the cells were specifically tested. The "ATCC" cells rapidly down-regulated the dopamine-transporter and...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research