Detection and quantification of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) from smoker albumin and its potential as a surrogate biomarker of tobacco-specific nitrosamines exposure and bioactivation
| Autor: | Yi Wang, Sreekanth C. Narayanapillai, Naomi Fujioka, Chengguo Xing, Qi Hu |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Nicotine Nitrosamines Time Factors Pyridines Toxicology Article Activation Metabolic Hemoglobins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tandem Mass Spectrometry medicine Humans Tobacco-specific nitrosamines Serum Albumin Carcinogen Smoking Albumin General Medicine Molecular biology Butanones Red blood cell 030104 developmental biology medicine.anatomical_structure chemistry Carcinogenic Nitrosamine Nitrosamine Case-Control Studies Models Animal Biomarker (medicine) Female Total Nicotine Equivalent Biomarkers 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Toxicol Lett |
| ISSN: | 0378-4274 |
| Popis: | 4-(Methylnitrosamino)-l-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), two tobacco specific nitrosamine carcinogens, can form adducts with DNA and proteins via pyridyloxobutylation upon phase I enzyme-mediated bioactivation. Such DNA modifications have been proposed as the root cause to initiate carcinogenesis. Upon hydrolysis, both DNA and protein modifications would release 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB). The released HPB, being tobacco carcinogen specific, has the potential to serve as a surrogate biomarker for both tobacco exposure and carcinogen bioactivation. Because of its easy access, blood is a great source of such investigations with the potential in epidemiological application. HPB quantification from haemoglobin (Hb), however, has been demonstrated with limited success. To further explore this potentially paradigm-shift opportunity, we reported, for the first time, the detection and quantification of HPB from albumin (Alb) adducts formed by the tobacco-specific nitrosamines in mice and in human smokers. The time-course quantitative analysis of HPB from mouse Alb upon NNK exposure suggests that such an Alb adduct is stable. The amounts of HPB from Alb adducts in smoker plasma averaged 1.82 ± 0.19 pg/mg Alb (0.42 to 3.11 pg/mg Alb), which was 36 times the value in nonsmokers (0.05 ± 0.01 pg/mg Alb). Importantly, HPB level from Alb correlated positively with the level of human tobacco exposure estimated by urinary total nicotine equivalent (TNE) (R2 = 0.6170). For comparison, HPB level from Alb was 16.5 times that of Hb (0.12 ± 0.02 pg/mg Hb) in the plasma and red blood cell (RBC) samples of the same smokers. In addition, there was no significant correlation between HPB levels from Hb and TNE (R2 = 0.0719). These data overall suggest that HPB from Alb adducts can serve as a surrogate biomarker to monitor the level of tobacco exposure and carcinogenic nitrosamine bioactivation. |
| Databáze: | OpenAIRE |
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