Formation of N-(2-hydroxyethyl)valine due to exposure to ethylene oxide via tobacco smoke: A risk factor for onset of cancer

Environ Res. 1999 Jul;81(1):62-71. doi: 10.1006/enrs.1998.3937.


Human exposure to ethylene oxide (EtO) occurs mainly through inhalation of occupational polluted air and tobacco smoke. EtO is able to react with DNA and proteins producing some molecular adducts. One of these, resulting from reaction between EtO and valine in hemoglobin, is N-(2-hydroxyethyl) valine (HOEtVal). This adduct represents a biological effective dose marker, the level of which correlates linearly with the alkylating activity occurring in DNA. The aim of the present study was to measure HOEtVal in 146 urbanized adult and healthy subjects, nonoccupationally exposed to EtO, and to correlate it with smoke habits. HOEtVal showed a direct positive relationship to tobacco smoke exposure quantified by questionnaire, urinary cotinine (r=0.64509), and the number of cigarettes (r=0. 6308) actively or passively smoked. Results relative to HOEtVal and urinary cotinine in adults distinguish well between active and passive smokers but do not allow distinguishment between passive smokers and nonsmokers. Nevertheless, several authors demonstrated a very good capacity of cotinine to discriminate inside groups of adolescents passive smokers. Therefore, the future objective of the present study is a closer inspection of the two biomarkers with respect to passive exposure to tobacco smoke considering a large group of adolescents. Finally, the correlation between urinary cotinine and HOEtVal increases knowledge about early steps of the carcinogenic process due to active exposure to tobacco smoke.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • Carcinogens / analysis
  • Cotinine / urine
  • Ethylene Oxide / analysis*
  • Ethylene Oxide / blood
  • Female
  • Gas Chromatography-Mass Spectrometry / methods
  • Hemoglobins / analysis
  • Humans
  • Male
  • Risk Factors
  • Smoking / blood
  • Smoking / urine
  • Surveys and Questionnaires
  • Tobacco Smoke Pollution / analysis*
  • Urban Population
  • Valine / analogs & derivatives*
  • Valine / blood


  • Biomarkers
  • Carcinogens
  • Hemoglobins
  • Tobacco Smoke Pollution
  • 2-hydroxyethylvaline
  • Valine
  • Ethylene Oxide
  • Cotinine