Carcinogenesis, Vol 19, 1763-1769, Copyright © 1998 by Oxford University Press
S Holt, TY Yen, R Sangaiah and JA Swenberg
The four etheno adducts of vinyl chloride formed in DNA, 1,N6-
ethenoadenine (epsilonA), 3,N4-ethenocytosine, 1,N2-ethenoguanine and
N2,3-ethenoguanine were previously reported to be released from DNA by a
family of enzymes in the base-excision repair pathway (Dosanjh et al.,
Proc. Natl Acad. Sci. USA, 91, 1024-1028, 1994; Hang et al.,
Carcinogenesis, 17, 155-157, 1996; Hang et al., Proc. Natl Acad. Sci. USA,
94, 12869-12874, 1997). Adducts excised from DNA by glycosylases are
usually excreted in urine and have been reported to be potential biomarkers
of DNA damage in exposed individuals. In this study, we report the
detection of epsilonA in the urine of rats exposed to chloroethylene oxide
(CEO) using immunoaffinity columns made with specific monoclonal antibodies
for enrichment, followed by quantitation by HPLC with fluorescence
detection. Chemical analysis of urine samples revealed the presence of a
compound chromatographically identical to authentic epsilonA standard. This
compound was confirmed by mass spectral analysis. EpsilonA was present in
urine of control and CEO- treated rats, with the latter having up to
50-fold greater amounts. The cumulative excretion of epsilonA reached a
plateau between 24 and 48 h post-exposure. While it is clear that CEO
treatment results in increased excretion of epsilonA, the exact source of
the adduct is unknown. When rats were administered epsilonA i.v.,
approximately 10% of the administered dose was excreted in urine. This
research demonstrates that urinary excretion of epsilonA may be a potential
biomarker for in vivo alkylation of DNA and nucleotide pools.
ARTICLES
Detection of 1,N6-ethenoadenine in rat urine after chloroethylene oxide exposure
Department of Environmental Sciences and Engineering and Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599-7400, USA.
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