Systematic Carcinogen Testing Through the Decision Point Approach

Williams, Gary M.; Weisburger, John H.

doi:10.1146/annurev.pa.21.040181.002141

Cited by 43 publications

(11 citation statements)

References 44 publications

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“…Attention is paid to qualitative-yes or no-answers, and to semiquantitative -high, medium or low -effects. The following outline has been described in detail with full literature citation (5,12 40, which bear such deactivation substituents on both sides of the azo bond, would be carcinogenic, and they have been found not mutagenic. On the other hand, more complex tetrazo dyes that include a potentially carcinogenic benzidine residue, available on biochemical reduction, are carcinogenic.…”

Section: The Decision Point Approachmentioning

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%

“…Andervont and Shimkin pioneered with the model involving the development of lung tumors in specific sensitive strains of mice, especially the A/Heston strain and related strains like A/J (1,12 Shay discovered, and Huggins extended, the finding that polycyclic hydrocarbons rapidly induced cancer in the mammary gland of young female random-bred Wistar rats and, to a greater degree, in Sprague-Dawley rats (1,4). With powerful carcinogens, especially select polycyclic hydrocarbons, arylamines, or nitrosoureas, a positive result is obtained in less than nine months.…”

Section: Pulmonary Tumor Induction In Micementioning

confidence: 99%

“…induced," transplanted, or metastatic neoplasms. 7 tential of chemicals (12). The key aim is to detect substances posing potential health risks, as well as to acquire knowledge as to which health risks are associated with which kinds of cancer, via the simplified, accelerated, more economical, and more reliable means afforded by the systematic decision point approach.…”

Section: Introductionmentioning

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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Section: The Decision Point Approachmentioning

confidence: 99%

Section: Battery Of Inmentioning

confidence: 99%

Section: Pulmonary Tumor Induction In Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Weisburger¹,

Williams²

1983

Environ Health Perspect

Self Cite

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show abstract

“…The best established are measurement of DNA binding of radiolabeled chemical (27) and the 32P-postlabeling technique for DNA adducts (39). The latter test revealed DNA binding by tamoxifen (16,17,32,48) but not by methapyrilene (8,26 (47,59).…”

Section: Introductionmentioning

confidence: 99%