Excess Number of Bladder Cancers in Workers Exposed to Ortho-Toluidine and Aniline

Ward, Elizabeth; Carpenter, Arvind V.; Markowitz, Steven; Roberts, Dennis R.; Halperin, William

doi:10.1093/jnci/83.7.501

Cited by 127 publications

(79 citation statements)

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“…In the early part ofthis century, industrial exposures to 4-aminobiphenyl (ABP), 2-naphthylamine, and benzidine were clearly associated with a high incidence oftransitional urothelial-cell carcinomas (5); recently, occupational exposures to 4,4'-methylenebis(2-chloroaniline) (MOCA) and o-toluidine have also been correlated with increased bladder cancer risk (6,7). Likewise, cigarette smoking has often been implicated as a causative factor in urinary bladder carcinogenesis (8); and this association has been supported by findings that aromatic amines such as ABP are present in nanogram quantities in cigarette smoke (9) and that smokers have much higher level of aromatic amine-hemoglobin adducts than nonsmokers (10).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

Kadlubar¹,

Butler²,

Kaderlik³

et al. 1992

Environmental Health Perspectives

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The metabolic pathways associated with carcinogenic aromatic amines in humans provide an excellent example of polymorphisms that appear to be relevant to human carcinogenesis. In this regard, the N-acetylation of arylamines and the O-acetylation of their N-hydroxy metabolites are catalyzed preferentially by a genetically polymorphic acetyltransferase, high activity of which has been correlated with decreased risk for urinary bladder cancer and increased susceptibility to colorectal cancer. Cytochrome P450IA2, the principal liver enzyme involved in aromatic amine N-oxidation, exhibits a wide interindividual variation that appears trimodal in several populations and is clearly inducible by cigarette smoking and probably other host factors as well. UDP-Glucuronosyltransferases, which catalyze the N-glucuronidation of N-hydroxyarylamines and are likely to be responsible for their transport to the colon, show widely varied but unimodal distributions in humans. In contrast, human liver sulfotransferase activity forN-hydroxyarylamines, which would be expected to decrease their transport through the circulation, is catalyzed by a polymorphic enzyme(s) that is expressed at higher levels in blacks, as compared to whites, and could contribute to their relatively lower incidence of urinary bladder cancer. Peroxidative activation of aromatic amines can also occur, especially from prostaglandin H synthase in the urinary bladder and myeloperoxidase in the lungs of cigarette smokers, and both show considerable individual variability, apparently due to the extent of tissue inflammation. In a pilot study, we have examined two of these polymorphisms, acetyltransferase and cytochrome P450IA2, in colorectal cancer/ polyp cases (n = 38) and controls (n = 100) and found that individuals who are both rapid acetylators and rapid N-oxidizers are indeed more prevalent (p < 0.008) among cases (37%) than among controls (16%).

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Section: Introductionmentioning

confidence: 99%

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

Kadlubar¹,

Butler²,

Kaderlik³

et al. 1992

Environmental Health Perspectives

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“…Despite the exclusion of the abovementioned carcinogenic arylamines, other aromatic amines continue to be used as textile dyes. Among them are aniline-based compounds and o-toluidine derivatives, which have been found to be correlated with increased bladder cancer risk 20,21) . In addition, environmental exposure to azo pigments, which are extensively used in textile factories, may result in internal exposure to aromatic amines which may be released by either reducing cleavage of azo bonds, or by hydrolysis of anilido bonds 22) .…”

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confidence: 99%

Urinary Mutagenicity, CYP1A2 and NAT2 Activity in Textile Industry Workers

Fanlo¹,

Sinués²,

Mayayo³

et al. 2004

Journal of Occupational Health

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Urinary Mutagenicity, CYP1A2 and NAT2 Activity in Textile Industry Workers: Ana FANLO, et al. Department of Pharmacology and Physiology, University of Zaragoza, Spain-The two major causes of bladder cancer have been recognised to be cigarette smoke and occupational exposure to arylamines. These compounds are present both in tobacco smoke and in the dyes used in textile production. Aromatic amines suffer oxidative metabolism via P450 cytochrome CYP1A2, and detoxification by the polymorphic NAT2. The aim of the present work was to assess the association between occupational-derived exposure to mutagens and CYP1A2 or NAT2 activity. This cross-sectional study included 117 textile workers exposed to dyes and 117 healthy controls. The urinary mutagenicity was determined in 24 h urine using TA98 Salmonella typhimurium strain with microsomal activation S9 (MIS9) or incubation with β-glucuronidase (MIβ). Urinary caffeine metabolite ratios: AFMU+1X+1U/17U, and AFMU/AFMU+1X+1U were calculated to assess CYP1A2 and NAT2 activities, respectively. The results show that workers present a strikingly higher urine mutagenicity than controls (p<0.0001), despite the implementation of the new restrictive norms forbidding the industrial use of the most carcinogenic arylamines. Neither NAT2 nor CYP1A2 activity had any effect on the markers of internal exposure to mutagens, since no significant differences were observed when the urinary mutagenicity of slow and fast acetylators (p>0.05) was compared, and the urinary mutagenicity was not significantly associated with the CYP1A2 activity marker (r=0.04 and r=-0.01 for MIS9 and MIβ, respectively). This study clearly indicates the need for further protective policies to minimise exposure to the Received May 10, 2004; Accepted Sep 6, 2004 Correspondence to: B. Sinués, Department of Pharmacology, Medicine School, University of Zaragoza, Domingo Miral s/n, 50009 Zaragoza, Spain (e-mail: bsinues@posta.unizar.es) lowest feasible limit in order to avoid unnecessary risks.

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“…The bladder carcinogenicity of several aromatic amines [2-naphthylamine, benzidine, 4-aminobiphenyl (7) and more recently ortho-toluidine (8) Given that such a disproportionately high number of human carcinogens have been identified in the workplace and that such a large number of animal carcinogens are found at high exposure levels in the occupational setting, how much of environmental cancer can be attributed to occupation? Is it 2-8%, as suggested by Doll and Peto in 1981 (20)?…”

Section: Occupational Cancermentioning

confidence: 99%

Use of rodent carcinogenicity test results for determining potential cancer risk to humans.

Infante

1993

Environ Health Perspect

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A high proportion of "human" and "probable human" carcinogens as categorized by the International Agency for Research on Cancer have been identified through observations in workers. The excess cancer risk has often been quite high. Most substances known to cause cancer in humans are now known to cause cancer in animals. In the past two decades, an increasing number of substances first shown to cause cancer in animals are now known to cause or are highly suspected of causing cancer in humans (and quite often in workers). The observations necessitate the use of rodent cancer test results for identifying and regulating potential environmental carcinogens. The role of cell proliferation (CP) in the carcinogenic response is important from a regulatory view in terms of both qualitative and quantitative evidence. If CP influences the carcinogenic response, the use of such data to modify dose response in the lowdose range is another factor that needs to be considered. Presentations at this symposium, however, indicate that CP data at the present time should not be incorporated into cancer risk assessments. More simple concepts that affect quantitative dose response and that may result in an artificially low estimated risk but could be adjusted for in the bioassay protocol have usually been ignored. A balanced approach would be to incorporate all known factors that influence quantitative estimates of cancer risk when conducting animal cancer bioassays and. extrapolating those results to humans.

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Excess Number of Bladder Cancers in Workers Exposed to Ortho-Toluidine and Aniline

Cited by 127 publications

References 0 publications

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

Urinary Mutagenicity, CYP1A2 and NAT2 Activity in Textile Industry Workers

Use of rodent carcinogenicity test results for determining potential cancer risk to humans.

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