In vitro and in vivo formation of 7-(2'-carboxyethyl)guanine from the liver carcinogen 1-nitroso-5,6-dihydrouracil and its reactions with water and methanol.
Base-catalyzed hydrolysis of the potent liver carcinogen 1-nitroso-5,6-dihydrouracil [(NDHU) CAS: 16813-36-8] afforded 3-hydroxypropionic acid and acrylic acid in 72 and 6% yield, respectively. The base-catalyzed methanolysis of NDHU gave quantitative yields of 3-methoxypropionic acid and methyl carbamate. These results indicate that base-catalyzed NDHU decomposition produces a 2-carboxyethyl carbonium-ion-type intermediate. When 3H-labeled NDHU was reacted at pH 8 with DNA and RNA, 7-(2'-carboxyethyl)guanine (CEG) was detected in the hydrolysate and was identified by its cochromatography with authentic CEG in five (for DNA) or three (for RNA) systems and by a reverse isotope-dilution procedure. Radioactively labeled CEG (identified as before) and five other labeled chromatographic fractions were present in liver DNA and RNA hydrolysates after [3H]NDHU was gavaged into MRC Wistar rats. These fractions persisted in the liver DNA for various times up to 33 days after the gavage. The CEG fraction was 94% of the radioactivity in DNA reacted in vitro, but it reached only 21% of the radioactivity in the liver DNA. The results are related to a study on single-strand breaks produced by NDHU in rat liver DNA.
Mirvish
S S
SS
Ross
A E
AE
Gold
B
B
Drake
N
N
D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D007553:Isotope Labeling; D008099:Liver / Q000378:metabolism*; D000432:Methanol / Q000378:metabolism*; D009602:Nitrosamines / Q000008:administration & dosage / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014867:Water / Q000378:metabolism*
D002273:Carcinogens; D009602:Nitrosamines; D014867:Water; C042808:7-(2-carboxyethyl)guanine; C011954:1-nitroso-5,6-dihydrouracil; D006147:Guanine; D012313:RNA; D004247:DNA; D000432:Methanol