Sulfotransferases: genetics and role in toxicology.
The mammalian xenobiotic-metabolizing sulfotransferases are cytosolic enzymes, which form a gene superfamily (SULT). Ten distinct human SULT forms are known. Two SULT forms represent splice variants, the other forms are encoded by separate genes. Common functional polymorphisms of the transcribed region 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 typhimurium TA1538 and/or V79 cells, which are target cells of commonly used mutagenicity assays. The expressed SULTs activated numerous compounds to mutagens in both assay systems. However, some promutagens were activated by only one or several of the human SULTs. Pronounced differences in promutagen activation were also detected between orthologous rat and human SULTs, and between allelic variants of human SULTs.
Glatt
H
H
Department of Toxicology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, D-14558, Potsdam-Rehbrücke, Germany. glatt@www.dife.de
Engelke
C E
CE
Pabel
U
U
Teubner
W
W
Jones
A L
AL
Coughtrie
M W
MW
Andrae
U
U
Falany
C N
CN
Meinl
W
W
D000818:Animals; D003001:Cloning, Molecular; D014644:Genetic Variation; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D011110:Polymorphism, Genetic; D051381:Rats; D012486:Salmonella typhimurium; D015238:Sulfotransferases / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014116:Toxicology
D009153:Mutagens; D015238:Sulfotransferases