Pyrroxamide, a nonionic nitroxyl spin label contrast agent for magnetic resonance imaging. Mutagenesis and cell survival.
Pyrroxamide [N-(1-hydroxymethyl-2,3-dihydroxypropyl)-2,2,5,5-tetramethyl pyrrolidine-1-oxyl-3-carboxyamide] is a newly tested nonionic monomeric nitroxyl compound with demonstrated effectiveness for MRI contrast enhancement at doses as low as 10(-3) M. Pyrroxamide and its hydroxylamine metabolic derivative were tested in concentrations from 10(-9) to 10(-2) M with a battery of cytotoxic and mutagenic assays using mammalian Chinese hamster ovary cells. Loci-specific mutation induction was examined at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and the Na+/K+ ATPase loci, both in the presence and absence of a liver microsomal metabolic activating mixture (S-9 mix). Cell survival and induction of sister chromatid exchanges also were studied. All tests yielded negative results indicating that pyrroxamide and and hydroxylamine derivative were both noncytotoxic and nonmutagenic at the doses tested.
Department of Radiology, University of California, San Francisco 94143-0628.
D G
DG
Gordon
R C
RC
Brasch
M D
MD
Ogan
D
D
Deen
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003287:Contrast Media / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005260:Female; D008279:Magnetic Resonance Imaging; D009154:Mutation; D010053:Ovary / Q000166:cytology / Q000187:drug effects*; D012854:Sister Chromatid Exchange / Q000187:drug effects
D003287:Contrast Media; D003497:Cyclic N-Oxides; C050028:N-1-hydroxymethyl-2,3-dihydroxypropyl-2,2,5,5-tetramethylpyrrolidin-1-oxyl-3-carboxamide