Sulfotransferases and acetyltransferases in mutagenicity testing: technical aspects.
Sulfotransferases (SULTs) and N-acetyltransferases (NATs) mediate the terminal activation step of various mutagens and carcinogens. Target cells of standard in vitro mutagenicity tests do not express any endogenous SULTs. NATs are expressed in some cells, but may not reflect the substrate specificity of human NATs. External activating systems usually lack the cofactors for these enzymes. Upon addition of the cofactor, the ultimate mutagen may be formed, but especially sulfo conjugates--anions--may not reliably penetrate into the target cells. This chapter presents methods used to incorporate these enzyme systems into in vitro mutagenicity test systems and to identify the critical human forms. The method of choice is direct expression of the enzymes in target cells. We present procedures on how this can be reached in bacteria and in mammalian cell lines in culture. Furthermore, genetically manipulated mouse models are a very promising perspective for answering open questions.
Glatt
Hansruedi
H
Department of Toxicology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
Meinl
Walter
W
D000123:Acetyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002474:Cell-Free System / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*; D011083:Polycyclic Compounds / Q000633:toxicity; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D011083:Polycyclic Compounds; D011994:Recombinant Proteins; D000123:Acetyltransferases; D015238:Sulfotransferases