Attomole Detection of 3H in Biological Samples Using Accelerator Mass Spectrometry: Application in Low-Dose, Dual-Isotope Tracer Studies in Conjunction with 14C Accelerator Mass

详细信息    查看全文

• 作者：Karen H. Dingley ; Mark L. Roberts ; Carol A. Velsko ; and Kenneth W. Turteltaub
• 刊名：Chemical Research in Toxicology
• 出版年：1998
• 出版时间：October 1998
• 年：1998
• 卷：11
• 期：10
• 页码：1217 - 1222
• 全文大小：65K
• 年卷期：v.11,no.10(October 1998)
• ISSN：1520-5010

文摘

This is the first demonstration of the use of accelerator mass spectrometry (AMS) as a toolfor the measurement of ³H with attomole (10^-18 mol) sensitivity in a biological study. AMS isan analytical technique for quantifying rare isotopes with high sensitivity and precision andhas been most commonly used to measure ¹⁴C in both the geosciences and more recently inbiomedical research. AMS measurement of serially diluted samples containing a ³H-labeledtracer showed a strong correlation with liquid scintillation counting. The mean coefficient ofvariation of ³H AMS based upon the analysis of separately prepared aliquots of these sampleswas 12%. The sensitivity for ³H detection in tissue, protein, and DNA was approximately2-4 amol/mg of sample. This high sensitivity is comparable to detection limits for ¹⁴C-labeledcarcinogens using ¹⁴C AMS and demonstrates the feasibility of ³H AMS for biomedical studies.One application of this technique is in low-dose, dual-isotope studies in conjunction with ¹⁴CAMS. We measured the levels of ³H-labeled 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP) and ¹⁴C-labeled 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in rat livertissue and bound to liver DNA and protein 4.5 h following acute administration of individualor coadministered doses in the range of 4-5100 pmol/kg of body weight. Levels of PhIP andMeIQx in whole tissue and bound to liver protein were dose-dependent. MeIQx-protein and-DNA adduct levels were higher than PhIP adduct levels, which is consistent with theirrespective carcinogenicity in this organ. Coadministration of PhIP and MeIQx did notdemonstrate any measurable synergistic effects compared to administration of these compoundsindividually. These studies demonstrate the application of AMS for the low-level detection of³H in small biological samples and for its use in conjunction with ¹⁴C AMS for dual-labelingstudies.