Molecular dosimetry of aromatic amines in human populations
Journal Article
·
· Environmental Health Perspectives
- Massachusetts Institute of Technology, Cambridge, MA (United States)
Certain aromatic amines carcinogenic for the human urinary bladder, such as 4-aminobiphenyl, undergo hepatic metabolic activation to N-hydroxylamines, which are transported to the bladder. During the transport process, these reactive species come in contact with hemoglobin and react with this blood protein. The principal hemoglobin adduct formed is a cysteine sulfinamide, and quantitative methods have been developed for the analysis of sulfinamide adducts at the levels present in ordinary human blood specimens. N-acetylation is an alternative metabolic fate to N-hydroxylation. The amount of hemoglobin adduct is decreased to the extent that this pathway is increased relative to N-hydroxylation. Thus, the hemoglobin adduct is sensitive to dose, cytochrome P-450-mediated activation, and N-acetyltransferase-mediated detoxification. In addition, it has been shown that DNA adduct concentration of 4-aminobiphenyl present in human bladder epithelial cells is significantly associated with hemoglobin adduct levels. Thus, the hemoglobin adduct of 4-aminobiphenyl, and perhaps several other aromatic amines, is a good dosimeter for the target tissue dose of the ultimate carcinogenic metabolite of these amines. Several studies have been undertaken in which the hemoglobin adducts of aminobiphenyls in human blood specimens were determined quantitatively. Information concerning exposure status and acetylator phenotype of the same individuals was obtained simultaneously. The results of these studies indicate that the hemoglobin adduct of 4-aminobiphenyl is closely associated with three major risk factors for bladder cancer; cigarette smoking, type of tobacco smoked, and acetylator phenotype. They also support a major etiologic role for aromatic amines in much of human bladder cancer. 42 refs., 4 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 478796
- Report Number(s):
- CONF-9210376--
- Journal Information:
- Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: Suppl.6 Vol. 102; ISSN 0091-6765; ISSN EVHPAZ
- Country of Publication:
- United States
- Language:
- English
Similar Records
Analytical methods for assessing exposure to 4-aminobiphenyl based on protein adduct formation
CYP1A2 and NAT2 phenotyping and 3-aminobiphenyl and 4-aminobiphenyl hemoglobin adduct levels in smokers and non-smokers
Smoking related carcinogen-DNA adducts in biopsy samples of human urinary bladder: Identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct
Journal Article
·
Fri Aug 01 00:00:00 EDT 1986
· JOM, J. Occup. Med.; (United States)
·
OSTI ID:5071193
CYP1A2 and NAT2 phenotyping and 3-aminobiphenyl and 4-aminobiphenyl hemoglobin adduct levels in smokers and non-smokers
Journal Article
·
Thu Jun 15 00:00:00 EDT 2006
· Toxicology and Applied Pharmacology
·
OSTI ID:20850342
Smoking related carcinogen-DNA adducts in biopsy samples of human urinary bladder: Identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct
Journal Article
·
Sat Jun 15 00:00:00 EDT 1991
· Proceedings of the National Academy of Sciences of the United States of America; (United States)
·
OSTI ID:6100129