Carcinogenesis Advance Access published online on February 23, 2006
Carcinogenesis, doi:10.1093/carcin/bgi362
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1 Institute of Environmental and Occupational Toxicology, Casella Postale 108, 6780 Airolo, Switzerland
* To whom correspondence should be addressed. Benzidine (Bz) is a known human carcinogen. Several azo dyes have been synthesized with Bz. Bz can be metabolically released from azo dyes. In a group of Indian workers producing Bz and azo dyes the presence of hemoglobin (Hb) adducts was investigated. The following Hb-adducts were identified and quantified by GC-MS: Bz, N-acetylbenzidine (AcBz), 4-aminobiphenyl (4ABP), aniline. 4ABP and aniline were quantitatively the major adducts. In the exposed workers (n=33) all correlations between 4ABP, Bz and AcBz are larger then r=0.89 (p<0.01). The group of workers exposed to Bz (Bz-workers, n=15) had 10-17-fold higher adduct levels than the workers exposed to dyes (dye-workers, n=18). 4ABP can be metabolically released from Bz and azo dyes. Aniline can be metabolically released from azo dyes. Therefore the presence of 4ABP and aniline as Hb-adducts is a consequence of exposure to the parent compounds or to the exposure of Bz and azo dyes and a consequent metabolical release of the arylamine moiety. The mean adduct ratios of 4ABP/(AcBz+Bz) varied up to 4-fold across all seven factories. Therefore it is possible that 4ABP may have derived from general contamination in the work environment or endogenous metabolism, or a combination of the two. Since 4ABP is also a known human carcinogen, tumors observed in workers exposed to Bz or Bz dyes might be caused by both compounds. Further, these results suggest that understanding the role that genetic variants in NAT1 and NAT2 play in modifying the impact of Bz on bladder cancer risk may be complicated, as N-acetylation detoxifies 4ABP and activates Bz.
Received August 19, 2005
Revised December 19, 2005
Accepted February 1, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Hemoglobin adducts in workers exposed to benzidine and azo dyes
Armin Beyerbach 1,
Nathaniel Rothman 2,
Vijai K. Bhatnagar 3,
Rekha Kashyap 3,
and
Gabriele Sabbioni 4 *
2 Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
3 National Institute of Occupational Health, Ahmedabad, India
4 Institute of Environmental and Occupational Toxicology, Casella Postale 108, 6780 Airolo, Switzerland; Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Nussbaumstrasse 26, 80336 München, Germany
Gabriele Sabbioni, E-mail: gabriele.sabbioni{at}bluewin.ch
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