Mutagenic decomposition products of nitrosated 4-chloroindoles.
4-Chloro-6-methoxyindole, a constituent of fava beans, forms a potent direct-acting mutagen, 4-chloro-6-methoxy-2-hydroxy-1-nitrosoindolin-3-one oxime, when nitrosated. In order to better understand the properties of this mutagen, we have studied a readily-available analog, 4-chloro-2-hydroxy-1-nitrosoindolin-3-one oxime, prepared by nitrosation of 4-chloroindole. This analog is also mutagenic, and both mutagens decompose rapidly at neutral or higher pH to yield in each case a new, less potent mutagen which then reacts further to form a nonmutagenic final product. The two products arising from 4-chloro-2-hydroxy-1-nitrosoindolin-3-one oxime, on the basis of comparison of spectroscopic and chromatographic evidence with that from authentic standards, are 4-chloro-N-nitrosodioxindole and 4-chloroisatin; those arising from 4-chloro-6-methoxy-2-hydroxy-1-nitrosoindolin-3-one oxime appear to be the corresponding 6-methoxy analogs. The interplay of these pathways with respect to net biological activity, especially under gastric conditions, remains to be described.
Brown
N K
NK
Division of Toxicology, Massachusetts Institute of Technology, Cambridge 02139.
Nguyen
T T
TT
Taghizadeh
K
K
Wishnok
J S
JS
Tannenbaum
S R
SR
D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000737:chemistry / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013056:Spectrophotometry, Ultraviolet
D007211:Indoles; D009153:Mutagens; D004247:DNA