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

Radiocarbon ◽  
1996 ◽  
Vol 38 (2) ◽  
pp. 347-353 ◽  
Author(s):  
X. S. Li ◽  
H. F. Wang ◽  
J. Y. Shi ◽  
X. Y. Wang ◽  
Y. F. Liu ◽  
...  

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.

Radiocarbon ◽  
1997 ◽  
Vol 39 (3) ◽  
pp. 293-297 ◽  
Author(s):  
X. H. Wu ◽  
H. F. Wang ◽  
Y. F. Liu ◽  
X. Y. Lu ◽  
J. J. Wang ◽  
...  

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.


2005 ◽  
Vol 20 (4) ◽  
pp. 397-401 ◽  
Author(s):  
H. F. Du ◽  
L. H. Xu ◽  
H. F. Wang ◽  
Y. F. Liu ◽  
X. Y. Tang ◽  
...  

2008 ◽  
Vol 36 (16) ◽  
pp. e100-e100 ◽  
Author(s):  
K. E. Coldwell ◽  
S. M. Cutts ◽  
T. J. Ognibene ◽  
P. T. Henderson ◽  
D. R. Phillips

2000 ◽  
Vol 126 (3) ◽  
pp. 171-183 ◽  
Author(s):  
Radoslav Goldman ◽  
Billy W Day ◽  
Tonya A Carver ◽  
Robert J Mauthe ◽  
Kenneth W Turteltaub ◽  
...  

Author(s):  
Kate Coldwell ◽  
Suzanne M. Cutts ◽  
Ted J. Ognibene ◽  
Paul T. Henderson ◽  
Don R. Phillips

1994 ◽  
Vol 40 (7) ◽  
pp. 1438-1443 ◽  
Author(s):  
P B Farmer

Abstract Exposure to genotoxic carcinogens results in the formation of covalently bound adducts of the carcinogens with cellular nucleophilic molecules, including DNA and protein. Quantitative measurements of these adducts may be used to monitor exposure to these carcinogens. The analytical methods required to detect the adducts need to be of exceptional sensitivity and include 32P-postlabeling, immunoassay, and physicochemical techniques (e.g., mass spectrometry or fluorescence measurements). Owing to its accessibility and long lifetime, hemoglobin is also suitable for carcinogen adduct measurement, and techniques based on gas chromatography-mass spectrometry or immunoassay have been developed for this purpose. Although the measurement of adducts is now accepted as a valid means of monitoring exposure to carcinogens, the value of such measurements in indicating carcinogenic risk in humans is less certain. However, adduct concentrations, particularly at low doses of carcinogen, have in several instances been shown to correlate with tumorigenicity in animal experiments.


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