Urinary markers for measuring exposure to endogenous and exogenous alkylating agents and precursors

Environ Health Perspect. 1993 Mar:99:33-7. doi: 10.1289/ehp.939933.

Abstract

Noninvasive methodologies for measuring carcinogen exposure in humans, based on the use of urinary markers, are being developed and validated for use in molecular epidemiological studies. A range of 3-alkyladenines can be determined in urine samples by an immunoaffinity purification-GC/MS approach [3-methyladenine, 3-ethyladenine, 3-(2-hydroxyethyl)adenine, and 3-benzyladenine]. Using this method, recent results in human subjects suggest that urinary 3-alkyladenines are potentially useful markers of alkylating agent exposure, particularly where the backgrounds of such adducts are much lower than 3-methyladenine. Urinary excretion of S-benzylmercapturic acid has been studied in experimental animals as a marker of exposure to benzylating agents such as N-nitroso-methylbenzylamine. 3-Nitrotyrosine (NTyr) is formed in vivo in tissue or blood proteins after exposure to nitrosating and/or nitrating agents such as tetranitromethane. After turnover of proteins, NTyr is released and excreted in urine as metabolites 3-nitro-4-hydroxy-phenylacetic acid and 3-nitro-4-hydroxyphenylacetic acid, which are determined by GC with a thermal energy analyzer. The sensitivity and specificity, combined with ease of use, of these noninvasive biomonitoring approaches means that they may be readily incorporated into molecular epidemiological studies in which exposure to nitrosating and alkylating agents may be important risk factors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / urine
  • Adenine / analogs & derivatives
  • Adenine / urine
  • Alkylating Agents / administration & dosage
  • Alkylating Agents / adverse effects*
  • Animals
  • Biomarkers / urine
  • DNA Damage*
  • Environmental Monitoring
  • Humans
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Alkylating Agents
  • Biomarkers
  • 3-nitrotyrosine
  • Tyrosine
  • Adenine
  • Acetylcysteine
  • S-benzyl-N-acetyl-L-cysteine