Mass spectrometric (MS)-based methods have been developed to measure biomarkers of exposure and DNA damage by heterocyclic aromatic amines (HAAs), carcinogens present in cooked meats, and by aristolochic acids (AAs), nephrotoxic and carcinogenic compounds found in Aristolochia herbaceous plants, used for medicinal purposes world-wide. Several of these biomarkers are being implemented in molecular epidemiology studies designed to establish the origin of human cancers for which an environmental cause is suspected. The uptake of the HAA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) into hair, its metabolites in urine, and DNA adducts in saliva and white blood cells of volunteers were determined following 4 weeks of consumption of well-done cooked meat. PhIP undergoes extensive bioactivation by cytochrome P450 1A2. The levels of PhIP in hair increased on average by 15-fold following consumption of cooked meat. However, PhIP accrual in hair did not correlate with P450 1A2 activity, or to the levels of unmetabolized PhIP and its major metabolites in urine. Salivary and white blood cell DNA adducts of PhIP were not detected; MS-based approaches are under development to measure PhIP-serum albumin adducts.  PhIP hair levels can serve as a biomarker in epidemiologic studies investigating the association of  HAAs, cooked meat, and cancer risk. MS approaches also are used to detect DNA adducts of AAs in freshly frozen or formalin fixed paraffin embedded (FFPE) kidney tissue, and in exfoliated urinary epithelial cells of individuals who have ingested certain traditional Chinese herbal medicines or products of wheat grain contaminated with Aristolochia seeds. AA-DNA adducts in FFPE kidney can be measured at level of 3 adducts per 109 DNA bases using only 2 �g of DNA.  We are exploring the usefulness of DNA from FFPE tissue and urinary epithelial cells  for the identification, by MS, of DNA adducts formed by other environmental and tobacco carcinogens.

New biospecimens and biomarker approaches for measuring exposures to environmental and dietary genotoxicants

248th National Meeting (2014)

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