A rapid in vitro assay for carcinogenicity of chemical substances in mammalian cells utilizing an attachment‐independence endpoint 2 – assay validation

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Abstract
In vitro carcinogenesis assays, in mammalian cells, are proving to be a necessary part of batteries of in vitro tests for detecting potential mutagens/carcinogens. The selection of which particular test to use requires an evaluation of test reliability, repeatability, sensitivity and degree of validation. Validation is particularly important because it is an integral part of the other criteria. Attachment independence is a common characteristic of transformed cells and is often used in follow‐up testing to confirm transformation. In an earlier report we described a transformation assay, the Survival Assay, which measures the acquisition of attachment independence. The Rauscher leukemia virus‐infected rat embryo target cells are treated with test compound for 72 h. Cells are then transferred to petri dishes containing a bottom layer of agar/medium. After 6 days the viable cell numbers of treated and control cultures are compared. We report here the results of testing 77 additional compounds in this assay; 73 of these were tested under code. Since definitive Carcinogenicity data were not available for 18 of the test compounds, it is not possible to list specific correlations with in vivo test results. None the less the assay correctly identified 44 of the 49 carcinogens and 7 of the 10 noncarcinogens in the list. The noncarcinogen status of two of the latter is, however, open to question. Thus the Survival Assay appears to provide information rapidly as to the potential carcinogenicity of a test material, even when subjected to validation testing with coded compounds.