High-sensitivity measurement of DNA adducts in germinal and somatic tissues by accelerator mass spectrometry
- Lawrence Livermore National Laboratory, CA (United States)
- SRI International, Menlo Park, CA (United States)
Accelerator Mass Spectrometry (AMS) is a nuclear physics technique developed in the mid-70`s for geochronology studies. AMS uses a low energy (kV) accelerator in tandem with a Van de Graaff electrostatic accelerator (mV) to separate and count nuclei of cosmogenic isotopes. AMS counts each nucleus particle by particle rather than relying on decay. This methodology difference results in a 10{sup 3}- to 10{sup 9}-fold improvement in isotope detection relative to decay counting, depending on the isotope. We have been developing AMS for use in assessing the pharmacokinetics and molecular effects of carcinogens, in both somatic and germinal tissues, at doses equivalent to human exposure levels. DNA adducts, using {sup 14}C-tagged carcinogens, have been measured at levels of 1 DNA adduct/10{sup 11} nucleotides. Effects of still lower doses can be assessed using animals which are raised to have 20% of the natural abundance of {sup 14}C which increased the signal-to-biological-noise-ratio of the analysis. We are also developing an AMS-radioimmunoassay with sensitivity on the order of 10-{sup 16}g thus eliminating the need to administer radiolabeled substances for human studies. AMS can also be used to measure other isotopes such as {sup 3}H, {sup 41}Ca, {sup 79}Se, {sup 53}Mn, and {sup 60}Fe. The high sensitivity of AMS for isotope detection in animal studies and the potential for its use in humans make AMS a valuable tool in the field of toxicology for assessing the short and long-term risks posed by chemicals and drugs to germinal and somatic cells.
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 88924
- Report Number(s):
- CONF-9405324-; ISSN 0893-6692; TRN: 95:004220-0070
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 23, Issue Suppl.23; Conference: 25. annual meeting of the Environmental Mutagen Society, Portland, OR (United States), 7-12 May 1994; Other Information: PBD: 1994
- Country of Publication:
- United States
- Language:
- English
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