73100-87-5Relevant articles and documents
A new LC-MS/MS method for the quantification of endogenous and vinyl chloride-induced 7-(2-oxoethyl)guanine in Sprague-Dawley rats
Mutlu, Esra,Jeong, Yo-Chan,Collins, Leonard B.,Ham, Amy-Joan L.,Upton, Patricia B.,Hatch, Gary,Winsett, Darrell,Evansky, Paul,Swenberg, James A.
, p. 391 - 399 (2012)
Vinyl chloride (VC) is an industrial chemical that is known to be carcinogenic to animals and humans. VC primarily induces hepatic angiosarcomas following high exposures (≥50 ppm). VC is also found in Superfund sites at ppb concentrations as a result of microbial metabolism of trichloroethylene and perchloroethylene. Here, we report a new sensitive LC-MS/MS method to analyze the major DNA adduct formed by VC, 7-(2-oxoethylguanine) (7-OEG). We used this method to analyze tissue DNA from both adult and weanling rats exposed to 1100 ppm [13C2]-VC for 5 days. After neutral thermal hydrolysis, 7-OEG was derivatized with O-t-butyl hydroxylamine to an oxime adduct, followed by (Figure presented) LC-MS/MS analysis. The limit of detection was 1 fmol, and the limit of quantitation was 1.5 fmol on the column. The use of stable isotope VC allowed us to demonstrate for the first time that endogenous 7-OEG was present in tissue DNA. We hypothesized that endogenous 7-OEG was formed from lipid peroxidation and demonstrated the formation of [13C2]-7-OEG from the reaction of calf thymus DNA with [13C18]-ethyl linoleate (EtLa) under peroxidizing conditions. The concentrations of endogenous 7-OEG in liver, lung, kidney, spleen, testis, and brain DNA from adult and weanling rats typically ranged from 1.0 to 10.0 adducts per 106 guanine. The exogenous 7-OEG in liver DNA from adult rats exposed to 1100 ppm [13C2]-VC for 5 days was 104.0 ± 23.0 adducts per 106 guanine (n = 4), while concentrations in other tissues ranged from 1.0 to 39.0 adducts per 10 6 guanine (n = 4). Although endogenous concentrations of 7-OEG in tissues in weanling rats were similar to those of adult rats, exogenous [ 13C2]-7-OEG concentrations were higher in weanlings, averaging 300 adducts per 106 guanine in liver. Studies on the persistence of [13C2]-7-OEG in adult rats sacrificed 2, 4, and 8 weeks postexposure to [13C2]-VC demonstrated a half-life of 7-OEG of 4 days in both liver and lung.
Synthesis of potential inhibitors of hypoxanthine-guanine phosphoribosyltransferase for testing as antiprotozoal agents. I. 7-Substituted 6-oxopurines
Piper,Laseter,Montgomery
, p. 357 - 364 (2007/10/02)
Biological evidence indicates that the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) (EC 2.4.2.8) is vital for cell proliferation in malarial parasites but nonessential for mammalian cells. 7-Substituted guanines and hypoxanthines in wh