Metabolism of arsenic in cultured cells.
Styblo M; Germolee D; Luster MI; Thomas DJ
Third International Conference on Arsenic Exposure and Health Effects, July 12-15, 1998, San Diego, California. Syracuse NY: The Society for Environmental Geochemistry and Health, 1998 Jul; :38
Although more experimental data are now available on the mechanisms of adverse effects of As in animal and human cell lines, little is known about the chemical and metabolic conversion that arsenicals undergo in cultured cells. The present work provides preliminary data on the metabolism of inorganic As (iAs) in selected cell lines, including human epidermal keratinocytes, HeLa (human cervical epithelioid carcinoma), rat primary hepatocytes and human primary hepatocytes. Among the cell lines examined, rat primary hepatocytes exhibited the greatest capacity for methylation of iAs. At nanomolar concentrations of iAs, these cells produced almost exclusively dimethyl As (DMAs); a small amount of methyl As (MAs) was detected in these cells. Yields of methylated metabolites increased with addition of up to 1 um iAs; however, the DMAs/MAs ratio was decreased. Production of MAs and DMAs was significantly suppressed in presence of 10 uM iAs and was almost abolished at 100 uM iAs. This suggested that the biomethylation of As was inhibited in a concentration-dependent manner. Methylation of iAs in HeLa cells yielded mostly MAs that was retained in cells. Addition of thiols stimulated efflux of MAs into the medium, suggesting that transport of this metabolite across the membrane could be thiol-dependent. Only a trace amount of MAs, but no DMAs, was detected in human keratinocytes that were incubated with iAs for 24 hours. Human primary hepatocytes isolated from tissue that was stored in preservation medium for 24 hours before perfusion were poor methylators of iAs. Here, MAs was the predominant metabolite. Taken together, the results indicate that there are important differences between cell lines in the capacity for methylation of iAs. Some of these differences may be species specific.
Metabolism; Arsenic-compounds; Arsenites; Cell-cultures; Laboratory-animals; Animals; Animal-studies
Miroslav Styblo, Ph. D., Department of Pediatrics, University of North Carolina at Chapel Hill, CB # 8180, Chapel Hill, NC 27599, USA
Abstract; Conference/Symposia Proceedings
Third International Conference on Arsenic Exposure and Health Effects, July 12-15, 1998, San Diego, California