Sulfotransferases: genetics and role in toxicology

The mammalian xenobiotic-metabolizing sulfotransferases are cytosolic enzym es, which form a gene superfamily (SULT). Ten distinct human SULT forms are known. Two SULT forms represent splice variants, the other forms are encod ed by separate genes. Common functional polymorphisms of the transcribed re gion are known for two of the forms. We have expressed 16 separate rat and human SULTs as well as some of their allelic variants, in Salmonella typhim urium TA1538 and/or V79 cells, which are target cells of commonly used muta genicity assays. The expressed SULTs activated numerous compounds to mutage ns in both assay systems. However, some promutagens were activated by only one or several of the human SULTs. Pronounced differences in promutagen act ivation were also detected between orthologous rat and human SULTs, and bet ween allelic variants of human SULTs. (C) 2000 Elsevier Science Ireland Ltd . All rights reserved.