Studies on DNA adduction with heterocyclic amines by accelerator mass spectroscopy (AMS): A new technique for tracing isotope labeled DNA adduction
Conference
·
OSTI ID:10157965
The influence of dose on the biological damage caused by exposure to xenobiotics has long been a subject of controversy in toxicology. Of particular recent interest has been the interaction of chemical carcinogens with DNA and the relationship between DNA adduction, chemical exposure, and cancer risk. We are studying DNA adduction in rodents at doses equivalent to human dietary exposure (10{sup 4}--10{sup 6}-fold lower than laboratory studies) using accelerator mass spectrometry (AMS). AMS is a nuclear physics technique for detection of cosmogenic isotopes and has been used for specifically selecting and counting {sup 14}C. Using AMS, DNA adducts are detectable at levels of 1--10 adducts/10{sup 12} nucleotides following acute and chronic dosing regimes with {sup 14}C-labeled carcinogens. The adduct detection limit has been imposed by the natural abundance of {sup 14}C in the samples and animal to animal variation. AMS is also being coupled to HIPLC, multi-dimensional TLC, and radio-immunoassay. In addition, AMS`s great sensitivity makes it useful for demonstrating that drugs and chemicals don`t bind DNA. The use of AMS, however, is limited to situations where radio-labeled agents can be used. These data suggest that AMS is extremely useful in obtaining quantitative data on the effects of carcinogens on DNA at the low doses common for actual human exposures and may be useful in human studies.
- Research Organization:
- Lawrence Livermore National Lab., CA (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 10157965
- Report Number(s):
- UCRL-JC--111534; CONF-9206374--1; ON: DE93012589
- Country of Publication:
- United States
- Language:
- English
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