1. Benzidine–DNA adduct levels in human peripheral white blood cells significantly correlate with levels in exfoliated urothelial cells
- Author
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Richard B. Hayes, Nathaniel Rothman, Terry V Zenzer, S. K. Kashyap, Qing Zhou, Rekha Kashyap, Bernard B. Davis, Glenn Talaska, V. K. Bhatnagar, Vijay M Lakshmi, Dinesh J Parikh, Mustafa Dosemeci, Marlene Jaeger, and Fong F. Hsu
- Subjects
Adult ,Urothelial Cell ,Health, Toxicology and Mutagenesis ,Urinary system ,India ,Adduct ,Toxicology ,Blood cell ,DNA Adducts ,chemistry.chemical_compound ,Occupational Exposure ,DNA adduct ,Leukocytes ,Genetics ,medicine ,Humans ,Carcinogen ,Benzidines ,Molecular biology ,Benzidine ,Cross-Sectional Studies ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,chemistry ,Toxicity ,Urothelium - Abstract
In a cross-sectional study of 33 workers exposed to benzidine and benzidine dyes and 15 non-exposed controls, we previously reported that exposure status and internal dose of benzidine metabolites were strongly correlated with the levels of specific benzidine-DNA adducts in exfoliated urothelial cells. We also evaluated DNA adduct levels in peripheral white blood cells (WBC) of a subset of 18 exposed workers and 7 controls selected to represent a wide range of adducts in exfoliated urothelial cells. Samples were coded and then DNA was analyzed using 32P-postlabeling, along with n-butanol extraction. One adduct, which co-chromatographed with a synthetic N-(3'-phospho-deoxyguanosin-8-yl)-N'-acetylbenzidine standard, predominated in those samples with adducts present. The median level (range) of this adduct in WBC DNA was 194.4 (3.2-975) RAL x 10(9) in exposed workers and 1.4 (0.1-6.4) in the control subjects (p = 0.0002, Wilcoxon Rank Sum Test). There was a striking correlation between WBC and exfoliated urothelial cell adduct levels (Pearson r = 0.84, p < 0.001) among exposed subjects. In addition, the sum of urinary benzidine, N-acetylbenzidine and N,N'-diacetylbenzidine correlated with the levels of this adduct in both tissues. This is the first study in humans to show a relationship for a specific carcinogen adduct in a surrogate tissue and in urothelial cells, the target for urinary bladder cancer.
- Published
- 1997
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