Analysis of DNA Adducts Formed in Vivo in Rats and Mice from 1,2-Dibromoethane, 1,2-Dichloroethane, Dibromomethane, and Dichloromethane Using HPLC/Accelerator Mass Spectrometry and Relevance to Risk Estimates†

Traditionally, the bioavailability of vitamin B-12 (B12) from in vivo labeled foods was determined by labeling the vitamin with radiocobalt (57Co, 58Co or 60Co). This required use of penetrating radioactivity and sometimes used higher doses of B12 than the physiological limit of B12 absorption. The aim of this study was to determine the bioavailability and absorbed B12 from chicken eggs endogenously labeled with 14C-B12 using accelerator mass spectrometry (AMS). 14C-B12 was injected intramuscularly into hens to produce eggs enriched in vivo with the 14C labeled vitamin. The eggs, which provided 1.4 to 2.6 μg of B12 (~1.1 kBq) per serving, were scrambled, cooked and fed to 10 human volunteers. Baseline and post-ingestion blood, urine and stool samples were collected over a one-week period and assessed for 14C-B12 content using AMS. Bioavailability ranged from 13.2 to 57.7% (mean 30.2 ± 16.4%). Difference among subjects was explained by dose of B12, with percent bioavailability from 2.6 μg only half that from 1.4 μg. The total amount of B12 absorbed was limited to 0.5–0.8 μg (mean 0.55 ± 0.19 μg B12) and was relatively unaffected by the amount consumed. The use of 14C-B12 offers the only currently available method for quantifying B12 absorption in humans, including food cobalamin absorption. An egg is confirmed as a good source of B12, supplying approximately 20% of the average adult daily requirement (RDA for adults = 2.4 μg/day).

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Genotoxicity Study on Nicotine and Nicotine-Derived Nitrosamine by Accelerator Mass Spectrometry

Radiocarbon ◽

10.1017/s0033822200017677 ◽

1996 ◽

Vol 38 (2) ◽

pp. 347-353 ◽

Cited By ~ 21

Author(s):

X. S. Li ◽

H. F. Wang ◽

J. Y. Shi ◽

X. Y. Wang ◽

Y. F. Liu ◽

...

Keyword(s):

Mass Spectrometry ◽

Dna Adducts ◽

Accelerator Mass Spectrometry ◽

Chemical Speciation ◽

Animal Experiments ◽

Tobacco Consumption ◽

Carcinogenic Risk ◽

Dna Adduction ◽

Carcinogenic Risk Assessment ◽

Potential Carcinogen

We have studied DNA adduction with 14C-labeled nicotine and nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by accelerator mass spectrometry (AMS) in mouse liver at doses equivalent to low-level exposure of humans. The dose ranges of nicotine and NNK administered were from 0.4 μg to 4.0×102 μg kg b.w.-1, and from 0.1 μg to 2.0×104 μg kg b.w.-1, respectively. In the exposure of mice to either nicotine or NNK, the number of DNA adducts increased linearly with increasing dose. The detection limit of DNA adducts was 1 adduct per 1011 nucleotide molecules. This limit is 1–4 orders of magnitude lower than that of other techniques used for quantification of DNA adducts. The results of our animal experiments enabled us to speculate that nicotine is a potential carcinogen. According to the procedure for 14C-labeled-NNK synthesis, we discuss the ultimate chemical speciation of NNK bound to DNA. From the animal tests we derived a directly perceivable relation between tobacco consumption and DNA adduction as the carcinogenic risk assessment.

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Histone Adduction with Nicotine: A Bio-Ams Study

Radiocarbon ◽

10.1017/s0033822200053273 ◽

1997 ◽

Vol 39 (3) ◽

pp. 293-297 ◽

Cited By ~ 16

Author(s):

X. H. Wu ◽

H. F. Wang ◽

Y. F. Liu ◽

X. Y. Lu ◽

J. J. Wang ◽

...

Keyword(s):

Mass Spectrometry ◽

Accelerator Mass Spectrometry ◽

Human Exposure ◽

Mouse Liver ◽

Dose Range ◽

The Other ◽

Histone 3 ◽

Protein Adduction ◽

Dna Adduction

Based on the study of DNA adduction with nicotine, we have measured the mouse hepatic histone adduction with 14C-labeled nicotine in vivo by bio-accelerator mass spectrometry (bio-AMS). In the exposure of mice to nicotine, the dose range administered was from 0.2 μg to 6.0 μg kg b.w.-1, which was equivalent to a very low level of human exposure to cigarette smoke. The adducts of either histone 1 (H1) or histone 3 (H3) with nicotine in mouse liver increased markedly with increasing nicotine dose. Our results have demonstrated that in the study of protein adduction with toxic xenobiotics as a biomarker, the AMS method achieves the highest sensitivity, 4.6 × 10-17 mol (46 amol) adducts per mg H1 protein, compared to all the other methods used previously.

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