An optimised data analysis for the Balb/c 3T3 cell transformation assay and its application to metal compounds. 2007

J Ponti, and B Munaro, and M Fischbach, and S Hoffmann, and E Sabbioni
European Commission, Joint Research Centre (JRC), Institute for Health and Consumer Protection, Ispra, Varese, Italy. jessica.ponti@jrc.it

The Balb/c3T3 cell transformation assay (CTA) is an available in vitro system to detect the carcinogenic potential of chemicals. Currently, the European Centre for the Validation of Alternative Methods (ECVAM) is validating this test, assessing its reliability and relevance. Its endpoint is the formation of type III foci, which is, when using clone A31-1-1, a very rare event that usually does not occur at all for negative controls. The carcinogenic potential of a compound tested is assessed by comparing the number of foci in treated and untreated cells. The objective of the present work is to optimise the data analysis for this endpoint by applying the most commonly used approach by a t-test and the Fisher's exact test as an alternative approach. For this purpose selected metal compounds classified as carcinogenic (NaAsO2, CdCl2, cisPt), as suspected carcinogenic (C6H5)4AsCl, CH3HgCl), or as compounds without evidence of carcinogenic properties in humans ((NH4)2PtCl6, NaVO3) as well as a non-carcinogenic (AgNO3) were analysed. Our evaluation revealed that the t-test approach, which assumes normality of data, is not appropriate. The results demonstrated that the statistical analysis by Fisher's exact test, better reflecting the data properties, greatly facilitates the interpretation of Balb/c3T3 CTA data regarding carcinogenic potential.

UI MeSH Term Description Entries
D008670 Metals Electropositive chemical elements characterized by ductility, malleability, luster, and conductance of heat and electricity. They can replace the hydrogen of an acid and form bases with hydroxyl radicals. (Grant & Hackh's Chemical Dictionary, 5th ed) Metal
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009942 Organometallic Compounds A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed) Metallo-Organic Compound,Metallo-Organic Compounds,Metalloorganic Compound,Organometallic Compound,Metalloorganic Compounds,Compound, Metallo-Organic,Compound, Metalloorganic,Compound, Organometallic,Compounds, Metallo-Organic,Compounds, Metalloorganic,Compounds, Organometallic,Metallo Organic Compound,Metallo Organic Compounds
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D003627 Data Interpretation, Statistical Application of statistical procedures to analyze specific observed or assumed facts from a particular study. Data Analysis, Statistical,Data Interpretations, Statistical,Interpretation, Statistical Data,Statistical Data Analysis,Statistical Data Interpretation,Analyses, Statistical Data,Analysis, Statistical Data,Data Analyses, Statistical,Interpretations, Statistical Data,Statistical Data Analyses,Statistical Data Interpretations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015197 Carcinogenicity Tests Tests to experimentally measure the tumor-producing/cancer cell-producing potency of an agent by administering the agent (e.g., benzanthracenes) and observing the quantity of tumors or the cell transformation developed over a given period of time. The carcinogenicity value is usually measured as milligrams of agent administered per tumor developed. Though this test differs from the DNA-repair and bacterial microsome MUTAGENICITY TESTS, researchers often attempt to correlate the finding of carcinogenicity values and mutagenicity values. Tumorigenicity Tests,Carcinogen Tests,Carcinogenesis Tests,Carcinogenic Activity Tests,Carcinogenic Potency Tests,Carcinogen Test,Carcinogenesis Test,Carcinogenic Activity Test,Carcinogenic Potency Test,Carcinogenicity Test,Potency Test, Carcinogenic,Potency Tests, Carcinogenic,Test, Carcinogen,Test, Carcinogenesis,Test, Carcinogenic Activity,Test, Carcinogenic Potency,Test, Carcinogenicity,Test, Tumorigenicity,Tests, Carcinogen,Tests, Carcinogenesis,Tests, Carcinogenic Activity,Tests, Carcinogenic Potency,Tests, Carcinogenicity,Tests, Tumorigenicity,Tumorigenicity Test
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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