Dm. Demarini et al., URINARY MUTAGENICITY AS A BIOMARKER IN WORKERS EXPOSED TO BENZIDINE -CORRELATION WITH URINARY METABOLITES AND UROTHELIAL DNA-ADDUCTS, Carcinogenesis, 18(5), 1997, pp. 981-988
Urinary mutagenicity has been used in occupational and epidemiological
studies for over two decades as a cost-effective, general biomarker o
f exposure to genotoxic agents. However, few studies have compared uri
nary mutagenicity to additional biomarkers determined among low- and h
igh-exposed groups. To address this issue, we evaluated the relationsh
ip between urinary mutagenicity and other types of biomarkers in a cro
ss-sectional study involving 15 workers exposed to the urinary bladder
carcinogen benzidine (BZ, high exposure), 15 workers exposed to BZ-dy
es (low exposure), and 13 unexposed controls in Ahmedabad, India. Urin
ary organics were extracted by C18/methanol and evaluated for mutageni
city in the presence of S9 in the Salmonella strain YG1024, which is a
frameshift strain that overproduces acetyltransferase. The results we
re compared to biomarker data reported recently from the same urine sa
mples (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 b
iomarker [a presumptive -(3'-phosphodeoxyguanosin-8-yl)-N'-acetylbenzi
dine (C8dG-ABZ) DNA adduct in exfoliated urothelial cells]. The mean S
E urinary mutagenicity (revertants/mu mol of creatinine) of the low-ex
posure (BZ-dye) workers was 8.2 +/- 2.4, which was significantly diffe
rent 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 presum
ptive C8dG-ABZ urothelial DNA adduct (r = 0.59, P = 0.0006). A strong
association was found between tobacco use (bidi smoking) and urinary m
utagenicity 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 exposur
es, identify additional genotoxic exposures among the controls, and co
rrelate strongly with urinary metabolites and DNA adducts in the targe
t tissue (urinary bladder epithelia) in humans.