Isolation and identification of a new mutagen, 2-amino-4-hydroxy-methyl-3,8-dimethylimidazo[4,5-f]quinoxaline (4-CH2OH-8-MeIQx), from beef extract.
By monitoring the mutagenicity to a new Salmonella tester strain, YG1024, which has a much higher level of O-acetyltransferase activity than S.typhimurium TA98, we found two new mutagenic compounds in bacteriological-grade beef extract. One of them (compound I), which had a similar UV spectrum to that of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), was isolated and shown to account for approximately 2% of the total mutagenicity of the materials adsorbed to blue cotton, and its concentration was estimated to be 6.0 ng/g beef extract. This amount of compound in beef extract was insufficient to allow measurements of various spectra, but its level was increased approximately 9-fold by heating beef extract with creatine and threonine at 200 degrees C for 5 h. From UV and mass spectra of the compound obtained from beef extract heated with creatine plus threonine, it was deduced to be a hydroxymethyl derivative of aminodimethylimidazo-quinoxaline. Compound I was isolated from the urine of rats given 4,8-DiMeIQx and identified as 2-amino-4-hydroxymethyl-3,8-dimethylimidazo[4,5-f]quinoxaline (4-CH2OH-8-MeIQx) by 1H-NMR analysis. 4-CH2OH-8-MeIQx induced 326,000 revertants of YG1024 and 99,000 revertants of TA98 per micrograms in the presence of S9 mix.
Kim
I S
IS
Carcinogenesis and Division, National Cancer Center Research Institute, Tokyo, Japan.
Wakabayashi
K
K
Kurosaka
R
R
Yamaizumi
Z
Z
Jinno
F
F
Koyota
S
S
Tada
A
A
Nukaya
H
H
Takahashi
M
M
Sugimura
T
T
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003401:Creatine / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008460:Meat / Q000032:analysis*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000302:isolation & purification* / Q000633:toxicity; D011810:Quinoxalines / Q000302:isolation & purification* / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D013056:Spectrophotometry, Ultraviolet; D013912:Threonine / Q000494:pharmacology; D014020:Tissue Extracts / Q000737:chemistry
D009153:Mutagens; D011810:Quinoxalines; D014020:Tissue Extracts; C085470:2-amino-4-hydroxymethyl-3,8-dimethylimidazo(4,5-f)quinoxaline; D013912:Threonine; D003401:Creatine; C045421:3,4,8-trimethylimidazo(4,5-f)quinoxalin-2-amine