Benzidine-DNA adduct levels in human peripheral white blood cells significantly correlate with levels in exfoliated urothelial cells.
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.
Zhou
Q
Q
Department of Environmental Health, University of Cincinnati, OH 45267-0056, USA.
Talaska
G
G
Jaeger
M
M
Bhatnagar
V K
VK
Hayes
R B
RB
Zenzer
T V
TV
Kashyap
S K
SK
Lakshmi
V M
VM
Kashyap
R
R
Dosemeci
M
M
Hsu
F F
FF
Parikh
D J
DJ
Davis
B
B
Rothman
N
N
D000328:Adult; D001560:Benzidines / Q000009:adverse effects / Q000378:metabolism*; D003430:Cross-Sectional Studies; D018736:DNA Adducts / Q000378:metabolism*; D006801:Humans; D007194:India; D007962:Leukocytes / Q000378:metabolism*; D016273:Occupational Exposure / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000139:chemically induced; D019459:Urothelium / Q000378:metabolism*
D001560:Benzidines; D018736:DNA Adducts; C029876:benzidine