Metabolism of Chemical Carcinogens

Weisburger, John H.; Williams, Gary M.

doi:10.1007/978-1-4615-6598-7_9

Cited by 15 publications

(16 citation statements)

References 231 publications

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“…16 Atmospheric oxygen is a principal chemical agent responsible for the weathering of coal, and low-rank coals react more readily with oxygen than high-rank coals, e.g., oxidation experiments on lignite samples showed that the formation of dihydroxybenzenes occurred during weathering. 85 Percolating surface water will also contribute to natural weathering processes and leach organic compounds, 85 and carcinogenic soluble organic compounds 86 are derived from the weathering of coals. 16 Therefore, weathered particles of lignite and shale in the unconsolidated alluvium from adjacent hills may contribute soluble toxic compounds to the groundwater in endemic villages.…”

Section: Spatial Correlation Is Nothing More Than Fortuitousmentioning

confidence: 99%

Limitations and plausibility of the Pliocene lignite hypothesis in explaining the etiology of Balkan endemic nephropathy

Maharaj¹

2013

International Journal of Occupational and Environmental Health

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Background: Balkan endemic nephropathy (BEN) is a chronic, tubulointerstitial renal disease often accompanied by urothelial cancer that has a lethality of nearly 100%. Introduction: One of the many factors that have been proposed to play an etiological role in BEN is exposure to organic compounds from Pliocene lignite coal deposits via the drinking water in endemic areas. Objectives: The objective of this study was to systematically evaluate the role of the tenets of the Pliocene lignite hypothesis in the etiology of BEN in order to provide an improved understanding of the hypothesis for colleagues and patients alike. Methods: A comprehensive compilation of the possible limitations of the hypothesis, with each limitation addressed in turn is presented. Results: The Pliocene lignite hypothesis can best account for, is consistent with, or has the potential to explain the evidence associated with the myriad of factors related to BEN. Conclusions: Residents of endemic areas are exposed to complex mixtures containing hundreds of organic compounds at varying doses and their potentially more toxic (including nephrotoxic) and/or carcinogenic metabolites; however, a multifactorial etiology of BEN appears most likely.

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Section: Spatial Correlation Is Nothing More Than Fortuitousmentioning

confidence: 99%

Limitations and plausibility of the Pliocene lignite hypothesis in explaining the etiology of Balkan endemic nephropathy

Maharaj¹

2013

International Journal of Occupational and Environmental Health

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“…AGE and other glycidyl ethers were mutagenic without microsomal activation in the TA100 strain of Salmonella typhimurium, but not in TA98 (41). AGE was nominated by NIOSH and OSHA for evaluation for carcinogenicity by the inhalation route because of the lack of information on its toxicity, the high potential for human exposure via inhalation, and its chemical structure (containing an epoxide ring and an allyl group), which suggests that it has the potential to form macromolecular adducts, possibly leading to cancer (42). The Following quarantine, 50 animals of each sex were assigned to each exposure and control group by randomization using body weight as a blocking variable (27) (27).…”

Section: Introductionmentioning

confidence: 99%

Morphology of Nasal Lesions Induced in Osborne-Mendel Rats and B6C3F1 Mice by Chronic Inhalation of Allyl Glycidyl Ether

1992

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Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epithelium and degeneration and regeneration with subsequent squamous and/or respiratory metaplasia of the olfactory epithelium were observed in many AGE-exposed animals. Three primary nasal neoplasms (1 papillary adenoma, 1 squamous cell carcinoma, and 1 olfactory epithelial carcinoma) were observed in rats exposed to 10 ppm AGE, and 1 nasal papillary adenoma was observed in a rat exposed to 5 ppm. Four papillary adenomas and 2 hemangiomas were observed in the noses of mice exposed to 10 ppm AGE. Although the incidence of primary nasal tumors in AGE-exposed rats or mice was not statistically significant compared to the incidence in concurrent controls, the relative rarity of primary nasal tumors in historical controls and the concurrent presence of metaplastic and hyperplastic nasal lesions similar to those reported to be associated with induced tumors of nasal epithelia by other chemicals suggest that the nasal tumors observed may be related to AGE exposure. It was concluded that, in addition to lesions indicating a toxic effect on the nasal mucosa, inhalation exposure to AGE for 24 months resulted in some evidence of carcinogenicity of AGE for male mice, equivocal evidence of carcinogenicity for female mice and male rats, and no evidence of carcinogenicity for female rats.

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“…Such chemicals are potential cancer risks mainly because they interfere with the normal physiological endocrine balance (24). More research on ways and means to quickly test for such properties is required.…”

Section: Decision Point 1: Summary Of Rapid In Vitro Testsmentioning

confidence: 99%

“…Adhering to these concepts, a battery of shortterm tests was proposed by Weisburger and Williams (4,12,20) as part of the "decision point approach." This battery includes a microbial mutagenesis test, because, thus far, such tests have been the most sensitive, effective, and readily performed screening tests.…”

Section: Battery Of Inmentioning

confidence: 99%

“…Few carcinogens-have yet been submitted to this technique, but based upon current knowledge of the pathogenesis of liver cancer, this is anticipated to be a highly reliable test for liver carcinogens. Since the liver is the target for so many carcinogens because of its metabolic capability (24), this test should possess substantial sensitivity.…”

Section: Altered Foci Induction In Rodent Livermentioning

confidence: 99%

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The distinct health risk analyses required for genotoxic carcinogens and promoting agents.

Weisburger¹,

Williams²

1983

Environ Health Perspect

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Health risk analysis needs to apply newer developments in the understanding of the underlying mechanisms of the carcinogenic process which has allowed for the classification of chemical carcinogens into those that damage genetic material directly (genotoxic carcinogens) and those that operate by indirect or epigenetic mechanisms. We propose a systematic decision point approach for detecting and evaluating substances for carcinogenic risk. This approach recognizes that genotoxic and epigenetic agents operate by different mechanisms and distinguishes between these two categories of carcinogens primarily on the basis of results in a battery of short-term tests that includes systems which reliably detect genotoxic carcinogens and others which may respond to epigenetic agents. Genotoxic carcinogens at very low dosages may have practical, effective threshold no-effect levels, but, nevertheless, because of their mechanism of action they are regarded as a qualitative hazard. The action of epigenetic agents of the promoter class is highly dose-dependent and reversible, and thus, a distinctively different health risk analysis is required for these agents to take account of their quantitatively lesser hazard.

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Metabolism of Chemical Carcinogens

Cited by 15 publications

References 231 publications

Limitations and plausibility of the Pliocene lignite hypothesis in explaining the etiology of Balkan endemic nephropathy

Limitations and plausibility of the Pliocene lignite hypothesis in explaining the etiology of Balkan endemic nephropathy

Morphology of Nasal Lesions Induced in Osborne-Mendel Rats and B6C3F1 Mice by Chronic Inhalation of Allyl Glycidyl Ether

The distinct health risk analyses required for genotoxic carcinogens and promoting agents.

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