Carcinogenesis, Vol 18, 981-988, Copyright © 1997 by Oxford University Press
DM DeMarini, LR Brooks, VK Bhatnagar, RB Hayes, BT Eischen, ML Shelton, TV Zenser, G Talaska, SK Kashyap, M Dosemeci, R Kashyap, DJ Parikh, V Lakshmi, F Hsu, BB Davis, M Jaeger and N Rothman
Urinary mutagenicity has been used in occupational and epidemiological
studies for over two decades as a cost-effective, general biomarker of
exposure to genotoxic agents. However, few studies have compared urinary
mutagenicity to additional biomarkers determined among low- and
high-exposed groups. To address this issue, we evaluated the relationship
between urinary mutagenicity and other types of biomarkers in a
cross-sectional study involving 15 workers exposed to the urinary bladder
carcinogen benzidine (BZ, high exposure), 15 workers exposed to BZ-dyes
(low exposure), and 13 unexposed controls in Ahmedabad, India. Urinary
organics were extracted by C18/methanol and evaluated for mutagenicity in
the presence of S9 in the Salmonella strain YG1024, which is a frameshift
strain that overproduces acetyltransferase. The results were compared to
biomarker data reported recently from the same urine samples (Rothman et
al., Proc. Natl Acad. Sci. USA, 93, 5084- 5089, 1996) that included a
metabolite biomarker (the sum of the urinary levels of BZ +
N-acetylbenzidine + N,N'-diacetylbenzidine) and a DNA adduct biomarker [a
presumptive N-(3'-phosphodeoxyguanosin-8-yl)- N'-acetylbenzidine (C8dG-ABZ)
DNA adduct in exfoliated urothelial cells]. The mean +/- SE urinary
mutagenicity (revertants/micromol of creatinine) of the low-exposure
(BZ-dye) workers was 8.2 +/- 2.4, which was significantly different from
the mean of the controls (2.8 +/- 0.7, P = 0.04) as was that of the mean of
the high-exposure (BZ) workers (123.2 +/- 26.1, P < 0.0001). Urinary
mutagenicity showed strong, positive correlations with urinary metabolites
(r = 0.88, P < 0.0001) and the level of the presumptive C8dG-ABZ
urothelial DNA adduct (r = 0.59, P = 0.0006). A strong association was
found between tobacco use (bidi smoking) and urinary mutagenicity among the
controls (r = 0.68, P = 0.01) but not among the exposed workers (r = 0.18,
P = 0.11). This study confirms the ability of a biomarker such as urinary
mutagenicity to detect low-dose exposures, identify additional genotoxic
exposures among the controls, and correlate strongly with urinary
metabolites and DNA adducts in the target tissue (urinary bladder
epithelia) in humans.
ARTICLES
Urinary mutagenicity as a biomarker in workers exposed to benzidine: correlation with urinary metabolites and urothelial DNA adducts
Environmental Carcinogenesis Division, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
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