Hydroxyethylvaline adduct formation in haemoglobin as a biological monitor of cigarette smoke intake

Abstract

The ethylene oxide adduct formed on the N-terminal valine in haemoglobin was investigated as a biological monitor of tobacco smoke intake. The modified method developed for the determination of the hydroxyethylvaline adduct (HOEtVal) involved reaction of globin with pentafluorophenyl isothiocyanate, extraction of the HOEtVal thiohydantoin product, derivatization of this by trimethylsilylation and quantitation by capillary gas chromatography with selective ion monitoring mass spectrometry using a tetradeuterated internal standard. The method was applied to globin samples from 26 habitual cigarette smokers and 24 non-smokers. There was a significant correlation between cigarette smoke intake as measured by the average number of cigarettes smoked per day and HOEtVal levels (r = 0.537, p less than 0.01). Background levels were found in non-smokers (mean 49.9 pmol/g Hb, range 22-106 pmol/g Hb). Smoking increased these levels by 71 pmol/g Hb/10 cigarettes per day. Cotinine levels in plasma of the smokers were determined by GC-NPD using 2-methyl-4-nitroaniline as internal standard. For non-smokers cotinine was determined by GC-MS selective ion monitoring using d3-methylcotinine as internal standard. There was no correlation between number of cigarettes smoked per day and cotinine levels (r = 0.297, p greater than 0.05) although cotinine was correlated with HOEtVal (r = 0.43, p less than 0.01). The HOEtVal adduct levels thus appear to be a suitable biomonitor for exposure to hydroxyethylating agents in cigarette smoke, reflecting an integrated dose over the erythrocyte lifetime. This is in contrast to plasma cotinine determinations which reflect only the previous day's exposure to nicotine in smoke.

Impact of smoking on the response to treatment of thyroid associated ophthalmopathy

“…There was a significant correlation between the average number of cigarettes smoked per day according to the patients and the HEV levels. The correlation coefficients from r = 0.56 to 0.60 are almost identical to those obtained by Bailey,12 and only slightly below the respective coefficient of r = 0.63 calculated by Bono et al 15 Bono et al also considered the contribution of passive smoking, which might explain the higher value obtained in their investigation. Thus, the method employed in this study proved to be suitable to estimate the influence of smoking on the response to TAO therapy and to investigate the dependence of this response on the extent of smoking.…”

“…Although other sources of ethylene oxide (that is, exhaust fumes, endogenous ethylene production 11 ) influence the HEV concentration, a linear relation between the number of cigarettes smoked per day and the HEV levels has been observed (correlation coefficient r = 0.54) indicating that HEV is a suitable biomarker for active and passive smoking. 12 …”

Monitoring human exposure to 2-hydroxyethylating carcinogens.

“…Of particular interest in these studies is that supposedly unexposed individuals contained background levels of HEV. Our initial sudies showed this background level to be at approximately 50 pmol HEV/g globin (11). In a more recent international study, we compared HEV levels in the globin of populations from four centers (York, U.K.; Swansea, U.K.; Mo, Norway; and Copenhagen, Denmark) (14).…”

Structural Characterisation of Acetaldehyde Adducts Formed by a Synthetic Peptide Mimicking the N‐Terminus of the Hemoglobin β‐Chain Under Reducing and Nonreducing Conditions

“…The current peptide sequence contains the Nterminal valine of the haemoglobin @-chain, which is known to form adducts with several compounds, i.e. glucose [26] and ethylene oxide [27]. There is previous evidence that acetaldehyde may also react with this residue [ l , 22, 281.…”