Studies on DNA adduction with heterocyclic amines by accelerator mass spectroscopy (AMS): A new technique for tracing isotope labeled DNA adduction

Conference · Tue Sep 29 04:00:00 EDT 1992

OSTI ID:6521814

Turteltaub, K W; Vogel, J S; Frantz, C E; Fultz, E

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: DOE; USDOE, Washington, DC (United States)
• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 6521814
• Report Number(s): UCRL-JC-111534; CONF-9206374--1; ON: DE93012589
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AMINES
AROMATICS
AZAARENES
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARCINOGENS
CHROMATOGRAPHY
DNA ADDUCTS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
POLYCYCLIC AROMATIC AMINES
SEPARATION PROCESSES
SPECTROSCOPY
TRACER TECHNIQUES