Evaluation of tobacco specific nitrosamines exposure by quantification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human hair of non-smokers.

Raúl Pérez-Ortuño,José A Pascual,Marcela Fu,Esteve Fernández,Jose M Martínez-Sánchez

doi:10.1038/srep25043

Abstract

Chronic exposure to specific carcinogens present in secondhand smoke has been associated with different types of cancers. Hair is an ideal matrix to develop a proper biomarker as it absorbs substances in circulation and allows measuring their average concentration over long periods of time. A method was developed for the simultaneous quantification of nicotine, cotinine, NNN, NNK and NNAL in 20 mg human hair samples. Concentrations were significantly different depending on the declared exposure. This study shows for the first time that NNK is present in hair samples from non-smokers in concentrations much higher than any other tobacco specific nitrosamine. NNN could also be detected in samples from the most exposed non-smokers while, as previously reported, NNAL was undetectable. NNK correlates well with nicotine and cotinine (rsp = 0.774 and rsp = 0.792 respectively, p < 0.001 in both cases). However, NNN concentrations did not correlate with any of the other analytes. Ratios between NNK and nicotine show variability with different concentrations of NNK present in samples with similar nicotine values. NNK has proven to be the best marker of tobacco specific nitrosamines in hair. Monitoring NNK may provide a good estimation of cancer risk associated with exposure to secondhand smoke.

Highlights

Exposure to secondhand tobacco smoke (SHS) increases the risk of respiratory and cardiovascular diseases[1,2] and it is classified as Group[1] carcinogen in humans by the International Agency for Research on Cancer (IARC)[1]
The evaluation of health risks linked with the exposure to SHS, and those associated with different types of cancer, has led research efforts to the study of Tobacco specific nitrosamines (TSNAs)
Exposure to tobacco specific carcinogens (i.e. TSNAs) has been regularly measured by quantifying total NNK and its main metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) in urine samples, it is known to represent less than 20% of the NNK dose intake in smokeless tobacco users[47]

Summary

Introduction

Exposure to secondhand tobacco smoke (SHS) increases the risk of respiratory and cardiovascular diseases[1,2] and it is classified as Group[1] carcinogen in humans by the International Agency for Research on Cancer (IARC)[1]. Exposure to SHS measured through hair analysis is less affected by the daily variability allowing a more robust comparison This is relevant when dealing with a non-smoker population, irregularly exposed to SHS27. NNAL has been detected in toenails and hair from regular smokers (i.e. more than 10 cigarettes per day) in concentrations ranging 0.04–4 pg/mg and 0.27–0.67 pg/mg respectively[41,42] It has been undetectable in samples from non-smokers[41]. NNN has been found in toenails from smokers and non-smokers in concentrations below 5 pg/mg[43] The objective of this project was the analysis of different tobacco specific biomarkers, including TSNAs, in hair samples from non-smokers in an attempt to find the best candidate. Considering the behaviour of nicotine and cotinine, the hypothesis was that NNK might be the most suitable hair biomarker of cumulative exposure to TSNAs

Objectives

Methods

Results

Conclusion