Grand
2
e Rounds
a shared dialogue among Occupational and Environmental Medicine Physicians,
the Hennepin Regional Poison Center, the Minnesota Department of Health,
and the University of Minnesota School of Public Health
Environmental Exposure Grand Rounds
Wednesday, May 13, 2015
Untapped biospecimens and strategies to measure exposures to
environmental carcinogens
Speaker:
Robert J. Turesky
Masonic Cancer Center and Department of Medicinal Chemistry,
University of Minnesota, Minneapolis, Minnesota 55455
Abstract:
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.
Studies were conducted on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant HAA
formed in cooked meat, by measuring the uptake of PhIP into hair, its metabolites in urine, and DNA adducts in
saliva and white blood cells of volunteers who consumed well-done cooked meat for 4 weeks. 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 have been established to quantitate DNA adducts of AAs in freshly frozen, but also formalin fixed
paraffin embedded (FFPE) kidney tissue and exfoliated urinary epithelial cells of individuals who have ingested
traditional Chinese herbal medicines contaminated with Aristolochia sp. FFPE tissue and exfoliated urinary cells are
largely untapped biospecimens to assess exposure to hazardous chemicals by measurement of DNA adducts. The
exquisite sensitive of MS instrumentation permits the measurement of AA-DNA adducts in tissues and urine at
levels as low as 3 adducts per 109 DNA bases using only 2 µg of DNA. We are exploring the usefulness of DNA from
FFPE tissue and exfoliated urinary cells for the identification, by MS, of DNA adducts formed by other
environmental and tobacco carcinogens.
Site Assessment and Consultation Unit
(651) 201-4897 or (800) 657-3908.
[email protected]
http://www.health.state.mn.us/divs/eh/hazardous/index.html