URINARY MARKERS FOR MEASURING EXPOSURE TO ENDOGENOUS AND EXOGENOUS ALKYLATING-AGENTS AND PRECURSORS

Noninvasive methodologies for measuring carcinogen exposure in humans, based on the use of urinary markers, are being developed and validate d for use in molecular epidemiological studies. A range of 3-alkyladen ines can be determined in urine samples by an immunoaffinity purificat ion-GC/MS approach 13-methyladenine. 3-ethyladenine, 3-(2-hydroxy-ethy l)adenine, and 3-benzyladenine]. Using this method, recent results in human subjects suggest that urinary 3-alkyladenines are potentially us eful markers of alkylating agent exposure, particularly where the back grounds of such adducts are much lower than 3-methyladenine. Urinary e xcretion of S-benzylmercapturic acid has been studied in experimental animals as a marker of exposure to benzylating agents such as N-nitros o-methylbenzylamine. 3-Nitrotyrosine (NTyr) is formed in vivo in tissu e or blood proteins after exposure to nitrosating and/or nitrating age nts such as tetranitromethane. After turnover of proteins, NTyr is rel eased and excreted in urine as metabolites 3-nitro-4-hydroxyphenylacet ic acid and 3-nitro-4-hydroxyphenylacetic acid, which are determined b y GC with a thermal energy analyzer. The sensitivity and specificity, combined with ease of use, of these noninvasive biomonitoring approach es means that they may be readily incorporated into molecular epidemio logical studies in which exposure to nitrosating and alkylating agents may be important risk factors.