Adducts of Acrylonitrile with Hemoglobin in Nonsmokers and in Participants in a Smoking Cessation Program

Abstract

Hemoglobin adducts have been used to assess exposure to carcinogenic compounds in tobacco smoke. However, because of background levels in nonsmokers, most adducts that have been studied are not useful for monitoring low-level exposure. Bergmark [(1997) Chem. Res. Toxicol. 10, 78-84] showed that the level of adducts of acrylonitrile (AN) with N-terminal valine (ANVal) increases with increasing cigarette consumption, and the increment from 1 cigarette/day was estimated to be 8 pmol/g of globin. The background level of ANVal in nonsmokers was not quantified (<2 pmol/g of globin). The objective of this study was to determine the background level of ANVal in hemoglobin and to study the stability of this adduct in vivo. Globin samples previously analyzed by Bergmark from 17 nonsmokers and 2 smokers were reanalyzed in the study presented here. Globin samples from 7 additional nonsmokers and from 10 participants in a smoking cessation program were also analyzed. Smoking habits and exposure to environmental tobacco smoke (ETS) were assessed by interview. Only two of the participants completed the program. The levels of ANVal in these 2 subjects decreased after quitting and were at background level by 126 days. The time course of the decrease was compatible with removal of stable adducts. The levels of ANVal in the nonsmokers were 0.76 +/- 0.36 (mean +/- SD) (n = 18; reporting no exposure ETS), 1.1 +/- 0.6 (n = 3; reporting exposure to ETS), and 1. 2 +/- 0.5 pmol/g of globin (n = 3; snuff users). Thus, the adduct level in nonsmokers corresponds to the adduct increment from about 0. 1 cigarette/day. Measurements of the level of ANVal could be used to distinguish between nonsmokers and low-level smokers on an individual level, but larger groups of individuals would be required to detect a possible contribution to the background from passive smoking.

Simultaneous quantification of haemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile, acrylamide and glycidamide in human blood by isotope-dilution GC/NCI-MS/MS

“…The levels of the other adducts investigated were obviously not affected by the exposure to passive smoke, probably due to variations in food patterns (AAVal, GAVal) as well as endogenous metabolism (HEVal, HPVal). This is in good agreement with the results of Perez et al [31] who reported CEVal-levels in blood of 3 passive smokers of 1.1 pmol/g globin as compared to 0.76 pmol/g globin in blood of 18 nonsmokers. An increased uptake (and excretion) of acrylonitrile in persons exposed to passive smoke could recently also be demonstrated using the excretion of the mercapturic acid of acrylonitrile (CEMA) as biomarker of exposure [32].…”

Molecular Mechanism of Acrylamide Neurotoxicity: Lessons Learned from Organic Chemistry

“…However, other sources of significant daily ACR exposure are now recognized, that is, air/water pollution, cigarette smoke, and diet (Friedman 2003; Perez et al 1999; Smith et al 2000; Tornqvist 2005; Tucek et al 2002). Although it has been estimated that the human body burden from these sources can be up to 30 μg ACR/kg/day (Food and Agriculture Organization of the United Nations and the World Health Organization 2005), the neurotoxicological significance of this exposure level is questionable (Boon et al 2005; Hagmar et al 2005; Kutting et al 2009).…”

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

“…Also acrylonitrile, a bulk chemical in elastomer and fiber production and a carcinogen present in active and passive tobacco smoke, is able to covalently bind proteins, such as at the N-terminal valine of hemoglobin (Pérez, Segerbaeck, & Osterman-Golkar, 1999). In vivo rat exposure and ex vivo studies on rat liver preparations highlighted binding to few specific proteins, identified as specific glutathione-S-transferase (Nerland et al, 2001) and carbonic anhydrase (Nerland, Cai, & Benz, 2003) isoenzymes.…”