title: Mutagenic and cell transformation activities of representative phosphorothioate esters in vitro.
abstract: Five alkyl and five aryl phosphorothioates are ranked relative to parathion in effectiveness as base-pair mutagens in the Ames mutagenic assay. Three in each series were mutagenic. Two commercial insecticidal phosphates, included for comparison, were mutagenic. The mutagenic phosphorothioates contained a strong electron-withdrawing and/or a good leaving group, together with two other groups small enough to permit nucleophilic attack by a biomacromolecule on the electrophilic phosphorus atom. All but one of the phosphorothioates [i.e., O,O,O-tris(2,2,2-trifluoro)ethyl phosphorothioate, VI] required metabolic activation for mutagenicity to be manifested; hence most of the phosphorothioates per se evidently are not ordinarily sufficiently electrophilic to be mutagenic but must instead be transformed to more electrophilic oxygen-containing products. In evaluation for cell-transformation properties, methyl parathion was inactive, in contrast to VI. The phosphorothioates that were novel were synthesized by formation of the phosphite from the appropriate alcohol or phenol, followed by reaction of the phosphite with sulfur.
mesh_terms: D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009946:Organothiophosphorus Compounds; D013329:Structure-Activity Relationship
chemical_list: D007306:Insecticides; D009153:Mutagens; D009946:Organothiophosphorus Compounds