In vitro sister chromatid exchange (SCE) and chromosome aberration (ABS) tests have been extensively used to identify potential rodent carcinogens. A number of measures of potency were developed to describe in vitro SCE and ABS test results: the dose needed to induce a unit increase over the control
Predicting rodent carcinogenicity from mutagenic potency measured in the Ames Salmonella assay
โ Scribed by Bethel A. Fetterman; Byung Soo Kim; Barry H. Margolin; Jonathan S. Schildcrout; Melissa G. Smith; S. Michelle Wagner; Errol Zeiger
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 103 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0893-6692
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โฆ Synopsis
Many in vitro tests have been developed to identify chemicals that can damage cellular DNA or cause mutations, and secondarily to identify potential carcinogens. The test receiving by far the most use and attention has been the Salmonella (SAL) mutagenesis test developed by Ames and colleagues [(1973): Proc Natl Acad Sci USA 70:2281-2285; (1975): Mutat Res 31:347-364], because of its initial promise of high qualitative (YES/NO) predictivity for cancer in rodents and, by extension, in humans. In addition to the initial reports of high qualitative predictivity, there was also an early report by Meselson and Russell [in Hiatt HH et al (1977): "Origins of Human Cancer, Book C: Human Risk Assessment," pp 1473-1481] of a quantitative relationship between mutagenic potency measured in SAL and carcinogenic potency measured in rodents, for a small number of chemicals. However, other reports using larger numbers of chemicals have found only very weak correlations. The primary purpose of this study was to determine whether mutagenic potency, as measured in a number of different ways, could be used to improve predictivity of carcinogenicity, either qualitatively or quantitatively. To this end, eight measures of SAL mutagenic potency were used. This study firmly establishes that the predictive relationship between mutagenic potency in SAL and rodent carcinogenicity is, at best, weak. When predicting qualitative carcinogenicity, only qualitative mutagenicity is useful; none of the quantitative measures of potency considered improves the carcinogenicity prediction. In fact, when qualitative mutagenicity is forced out of the model, the quantitative measures are still not predictive of carcinogenicity. When predicting quantitative carcinogenicity, several possible methods were considered for summarizing potency over all experiments; however, in all cases, the relationship between mutagenic potency predictors and quantitative carcinogenicity is very weak.
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