Chemical mutagens activation

Mutagenic and later carciaogenic properties were found for tris(2,3-dibromopropyl) phosphate (148—150), a flame retardant used on polyester fabric ia the 1970s. This product is no longer on the market. The chemically somewhat-related tris(dichloroisopropyl) phosphate has been intensively studied and found not to display mutagenic activity (148,149,151). Tris(2-chloroethyl) phosphate appears to be a weak tumor-iaducer ia a susceptible rodent strain (150). 

NCI. 1968. Evaluation of carcinogenic, teratogenic and mutagenic activities of selected pesticides and industrial chemicals. Volume I Carcinogenic study. Prepared by Bionetics Research Labs, Inc., Bethesda, MD National Cancer Institute. NCI-DCCP-CG-1973-1-1. 

Simmon VF, Rosenkranz HS, Zeiger E. et al. 1979. Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host- mediated assay. J Nat Cancer Inst 62 911-918. 

Khudoley W, Mizgireuv I, Pliss GB. 1987. The study of mutagenic activity of carcinogens and other chemical agents with Salmonella typhimurium assays Testing of 126 compounds. Arch Geschwulstforsch 57 453-462. 

Many plasmids are known to possess three properties (1) increased resistance to the bactericidal effects of UV and chemical mutagens, (2) increased spontaneous mutagenesis, and (3) increased susceptibility to UV and chemically induced mutagenesis. Some plasmids possess all three properties others may possess just one, for example, increased susceptibility to mutagenesis (review Mortelmans and Dousman, 1986). Often the profile of activity depends on the DNA repair status of the host cell (Pinney, 1980). Plasmid pKMIOl carries DNA repair genes and has been widely used in strains used in bacterial mutagenicity tests. 

In the bacterial mutation test, the mutagenic potential of a pharmaceutical and its metabolites is evaluated by measuring and quantifying its ability to induce reverse mutations at selected loci of Salmonella typhimurium or Escherichia coli in the presence and absence of metabolic activation. This test system has been shown to detect a diverse group of chemical mutagens.3,4 The technical details of this test have been reported in the literature.5-7... 

Simmon VF, Kauhanen K, Tardiff RG. 1977. Mutagenic activity of chemicals identified in drinking water. Dev Toxicol Environ Sci 1 249-258. 

Bignami M, Cardamone, G, Comba P, et al. 1977. Relationship between chemical structure and mutagenic activity in some pesticides The use of Salmonella typhimurium and Aspergillus nidulans. Mutat Res 46 243-244. 

Buijs W, Van der Gen A, Mohn GR, et al. 1984. The direct mutagenic activity of alpha, omega-dihalogenoalkanes in Salmonella typhimurium. Strong correlations between chemical properties and mutagenic activity. Mutat Res 141 11-14. 

Hughes TJ, Simmons DM, Monteith LG, et al. 1987. Vaporization technique to measure mutagenic activity of volatile organic chemicals in the Ames/ Salmonella assay. Environ Mutagen 9 421-441. 

Kerklaan PRM, Zoetemelk CEM, Mohn GR. 1985. Mutagenic activity of various chemicals in Salmonella strain TA100 and glutathione-deficient derivatives On the role of glutathione in the detoxification or activation of mutagens inside bacterial cells. Biochem Pharmacol 34 2151-2156. 

H. J. Muller s discovery in 1927 that radiation could induce mutations in living organisms. Whether congenital diseases such as Down s syndrome (in which an extra copy of a particular chromosome, or aneu-ploidy, is present) are much influenced by chemical mutagens in the environment remains an active area of study by genetic toxicologists. 

An extensive database has demonstrated that many chemicals that are positive in this test also exhibit mutagenic activity in other tests. There are, however, examples of mutagenic substances, which are not detected by this test reasons for these shortcomings can be ascribed to the specific nature of the endpoint detected, differences in metabolic activation, or differences in bioavailability. On the other hand, factors which enhance the sensitivity of the bacterial reverse mutation test can lead to an overestimation of mutagenic activity. The bacterial reverse mutation test may not be appropriate for the evaluation of certain classes of chemicals for example, highly bactericidal compounds (e.g., certain antibiotics) and those which are thought (or known) to interfere specifically with the mammalian cell replication system (e.g., some topoisomerase inhibitors and some nucleoside analogues). In such cases, mammalian mutation tests may be more appropriate. 

National Cancer Institute Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals, Vol I. Carcinogenic Study, 1968... 

Blakey DH, Mans KL, Bell R, et al Mutagenic activity of 3 industrial chemicals in a battery of in vitro and in vivo tests. Mutat Res 320 273-283, 1994... 

Rinkus SJ, Legator MS. 1979. Chemical characterization of 465 known or suspected carcinogens and their correlation with mutagenic activity in the Salmonella typhimurium system. Cancer Res 39 3289-3318. 

Gundel, L. A., J. M. Daisey, L. R. F. de Carvalho, N. Y. Kado, and D. Schuetzle, Polar Organic Matter in Airborne Particles Chemical Characterization and Mutagenic Activity, Environ. Sci. Technol., 27, 2112-2119 (1993). 

Butler, J. P., T. J. Kneip, and J. M. Daisey, An Investigation of Interurban Variations in the Chemical Composition and Mutagenic Activity of Airborne Particulate Organic Matter Using an Integrated Chemical Class/Bioassay System, Atmos. Environ., 21, 883-892 (1987). 

Chemical Characterization and Mutagenic Activity, Environ. Sci, Technol., 27, 2112-2119 (1993). 

Hughes, T. J., D. M. Simmons, L. G. Monteith, and L. D. Claxton, Vaporization Technique to Measure Mutagenic Activity of Volatile Organic Chemicals in the Ames/Salmonella Assay, Environ. Mutagen., 9, 421-441 (1987). 

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