Analysis of 7-methylguanine using isotope dilution and gas chromatography/electron-capture negative chemical ionization mass spectrometry.
This paper presents results obtained for in vivo endogenous and exogenous 7-methylguanine (7-MG) analyzed using a method incorporating gas chromatography with electron-capture negative chemical ionization mass spectrometry and isotope dilution (GC/EC-ID-MS). 13C4-Labeled 7-MG was synthesized to serve as an internal standard to improve accuracy of quantitation, and was used to analyze 7-MG in livers of control mice and dacarbazine-treated mice. The results confirm that 7-MG in tissue DNA can be measured using this GC/EC-ID-MS method with excellent sensitivity and specificity. Administration of 0, 30, and 60 mg/kg dacarbazine to mice led to dose-dependent increases in the formation of 7-MG. The results indicate that this method could be applied to the analysis of endogenous and exogenous 7-MG in human tissues for future molecular epidemiology studies on potential health effects caused by methylating agents.
Chiang
Su-Yin
SY
Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan.
Huang
Tai-Hung
TH
Uang
Shi-Nian
SN
Wu
Hong-Dar Isaac
HD
Wei
Yi-Chiech
YC
Lin
Hui-Yi
HY
Swenberg
James A
JA
Wu
Kuen-Yuh
KY
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002247:Carbon Isotopes; D018736:DNA Adducts / Q000032:analysis; D003606:Dacarbazine / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000592:standards; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D018906:Antineoplastic Agents, Alkylating; D002247:Carbon Isotopes; D018736:DNA Adducts; D006147:Guanine; C008450:7-methylguanine; D003606:Dacarbazine