Studies on DNA adduction with heterocyclic amines by accelerator mass spectrometry: a new technique for tracing isotope-labelled DNA adduction.
DNA adduction in rodents at doses equivalent to human dietary exposure (10(4)-10(6)-fold lower than laboratory studies) is being studied 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 14C. Using AMS, DNA adducts are detectable at levels of 1-10 adducts/10(12) nucleotides following acute and chronic dosing regimes with 14C-labelled carcinogens. The adduct detection limit has been imposed by the natural abundance of 14C in the samples and animal-to-animal variation. AMS is also being coupled to HPLC, multidimensional TLC and radio-immunoassay. In addition, AMS's great sensitivity makes it useful for demonstrating that drugs and chemicals do not bind to DNA. The use of AMS, however, is limited to situations where radiolabelled agents can be used. The 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.
Turteltaub
K W
KW
Biomedical Sciences Division, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Vogel
J S
JS
Frantz
C E
CE
Fultz
E
E
D000588:Amines / Q000633:toxicity*; D000818:Animals; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000633:toxicity; D004247:DNA / Q000032:analysis* / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data; D011804:Quinolines / Q000633:toxicity; D051381:Rats; D012680:Sensitivity and Specificity
D000588:Amines; D002250:Carbon Radioisotopes; D002273:Carcinogens; D011804:Quinolines; D004247:DNA; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline