URINARY MUTAGENICITY AS A BIOMARKER IN WORKERS EXPOSED TO BENZIDINE -CORRELATION WITH URINARY METABOLITES AND UROTHELIAL DNA-ADDUCTS

Citation
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
Citations number
71
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
ISSN journal
0143-3334
Volume
18
Issue
5
Year of publication
1997
Pages
981 - 988
Database
ISI
SICI code
0143-3334(1997)18:5<981:UMAABI>2.0.ZU;2-B
Abstract
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.