Genetic toxicology assays

The nature of the toxicological endpoint to be measured. Some endpoints are more readily measured in certain cell types or cell lines. For example, the human hepatoma cell line HepG2 forms colonies with very low efficiency. Therefore some genetic toxicology assays, such as the induction of gene locus mutations, cannot be easily measured in this cell line. 

Resorcinol is water-soluble and readily conjugated and eliminated. The chemical has no known potential for formation of electrophilic reactive intermediates comparable to those derived from the other dihydroxybenzenes. Resorcinol was tested in various genetic toxicology assays, including in-vitro bacterial and mammalian assays and in-vivo mammalian assays. It gave negative results in all studies, with the exception of a positive response in the two in-vitro studies that assessed chromosomal aberrations in human lymphocytes from whole blood cultures however, resorcinol did not induce chromosomal aberrations in human fibroblasts. 

Endpoints Used for In Vivo Genetic Toxicology Assays... 

Mackay, J. M. (1995). Dose selection in in vivo genetic toxicology assays. Environ Mol Mutagen 25, 323-327. 

Natarajan, A.T. and Obe, G. (1982). Mutagenicity testing with cultured mammalian cells cytogenetic assays. In Mutagenicity, New Horizons in Genetic Toxicology, (Heddle, J.A., Ed.). Academic Press, New York, pp. 172-213. 

Parry, J.M., Arlett, C.F. and Ashby, J. (1985). An overview of the results of the in vivo and in vitro test systems used to assay the genotoxicity of BZD, DAT, DAB and CDA in the second UKEMS study. In Comparative Genetic Toxicology The Second UKEMS Collaborative Study, (Parry, J.M. and Arlett, C.F., Eds.). Macmillan, London, pp. 597-616. 

The weight of evidence from in vivo and in vitro genetic toxicology tests, in vivo liver function studies, and the two-stage tumor promotion assay is adequate to conclude that chlordecone is a promotor rather than an initiator of carcinogenesis. While the evaluation of mirex in an in vivo tumor promoter... 

Genotoxicity. No definite conclusions can be reached from the in vitro human cell and whole animal genetic toxicology studies that have been performed with fuel oils. Data from bacterial in vitro assays are inconsistent (see Section 2.4, Genotoxic Effects). A study of the genotoxicity/mutagenicity of commercially available fuel oils and the various component petroleum streams used in their formulation would be of value. 

Genetic Toxicology In Vitro Sister Chromatid Exchange Assay in Mammahan Cells (Original Guideline, adopted 23 October 1986)... 

Genetic toxicology Mouse heritable translocation assay... 

Genetic toxicology In vitro sister chromatid exchange assay in mammalian cells 1986... 

Genetic toxicology Saccharomyces cerevisiae, gene mutation assay 1986... 

H., Miyamae, Y, Rojas, E. et al. (2000) Single cell gel/comet assay guidelines for in vitro and in vivo genetic toxicology testing. Environmental and Molecular Mutagenesis, 35, 206-221. 

There are few data available on the genetic toxicology of 5-chloro-ori/70-toluidine. In single assays, it did not induce mutagenicity in Salmonella typhimurium, prophage lambda in Escherichia coli or unscheduled DNA synthesis in cultured rat hepatocytes. 

Lofroth, G, Nilsson, L. Andersen, J.R. (1986) Stracture-activity relationship of nitroalkane-induced mutagenicity in the Ames Salmonella assay. Genetic toxicology of environmental chemicals, Part B Genetic effects and applied mutagenesis. Prog. din. biol. Res., 209B, 149-155... 

Wyrobek AJ (1982) Sperm assays as indicators of chemically-induced germ ceil damage in man. In Heddle JA ed. Mutagenicity New horizons in genetic toxicology. New York, Academic Press, pp 337-349. 

A brief overview of major assay systems in genetic toxicology is presented in Table 5-1. The inclusion of particular assays is somewhat subjective. Nevertheless, the table provides ready reference to the major assays, including all those discussed in this report. 

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