Urinary mutagenicity as a biomarker in workers exposed to benzidine: Correlation with urinary metabolites and urothelial DNA adducts

David M. DeMarini, Lance R. Brooks, V. K. Bhatnagar, Richard B. Hayes, Brent T. Eischen, Melissa L. Shelton, Terry V. Zenser, Glenn Talaska, S. K. Kashyap, Mustafa Dosemeci, Rekha Kashyap, Dinesh J. Parikh, V. Lakshmi, F. Hsu, B. B. Davis, Marlene Jaeger, Nathaniel Rothman

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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 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/μmol 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.

Original languageEnglish
Pages (from-to)981-988
Number of pages8
JournalCarcinogenesis
Volume18
Issue number5
DOIs
StatePublished - May 1997

Fingerprint

Dive into the research topics of 'Urinary mutagenicity as a biomarker in workers exposed to benzidine: Correlation with urinary metabolites and urothelial DNA adducts'. Together they form a unique fingerprint.

Cite this