Carcinogenesis Advance Access originally published online on February 23, 2006
Carcinogenesis 2006 27(8):1600-1606; doi:10.1093/carcin/bgi362
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Hemoglobin adducts in workers exposed to benzidine and azo dyes
1 Institute of Environmental and Occupational Toxicology Casella Postale 108, CH-6780 Airolo, Switzerland
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, 20892, USA
3 National Institute of Occupational Health Ahmedabad, India
4 Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München Nussbaumstrasse 26, 80336 München, Germany
*To whom correspondence should be addressed at: Institute of Environmental and Occupational Toxicology, Casella Postale 108, CH-6780 Airolo, Switzerland. Email: gabriele.sabbioni{at}bluewin.ch
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 were r = 0.89 (P < 0.01) or greater. 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.
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