Responses of the L5178Y tk⁺/tk⁻ mouse lymphoma cell forward mutation assay to coded chemicals. I: Results for nine compounds

Abstract

Nine substances were tested for their mutagenic potential in the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay, by means of procedures based upon those described by Clive and Spector (Mutat Res 44:269-278, 1975) and Clive et al (Mutat Res 59:61-108, 1979). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The coded chemicals were tested at least twice. Significant responses were obtained with calcium chromate, 3-(chloromethyl)pyridine, 1,2-epoxybutane, monochloroacetic acid, dicyclohexylthiourea, 2,4-diaminophenol hydrochloride, and pentachloroanisole. Apart from pentachloroanisole, rat liver S9 mix was not a requirement for the clearly mutagenic activity of any of these compounds. Compounds not identified as mutagens were 3-amino-1,2,4-triazole and sucrose.

Scientific Opinion on the risks to public health related to the presence of chromium in food and drinking water

“…Cr(VI) compounds are also mutagenic in mammalian cell lines. Potassium dichromate was reported to significantly increase mutation frequency at the HPRT locus in Chinese hamster cells AT3-2 and V79 (Paschin et al, 1983), and calcium chromate at the TK locus in mouse lymphoma cells L5178Y (McGregor et al, 1987). Clastogenic activity (micronuclei, chromosomal aberrations and sister chromatid exchanges) of Cr(VI) compounds (i.e.…”

An evaluation of the mode of action framework for mutagenic carcinogens case study II: Chromium (VI)

“…Microbial data compiled from the work of NTP [2008], Haworth et al [1983], and Watanabe et al [1998] are presented in Table I and illustrate the point that Cr (VI) induces a clear linear concentration response in mutant colonies at nonactivated concentrations down to relatively lownoncytotoxic levels in bacterial strains (S. typhimurium and E. coli), which are sensitive to agents inducing base pair substitutions, point mutations, as well as oxidative damage and DNA crosslinks. It is also mutagenic in Saccharomyces cerevisae [Singh, 1983] and in mammalian cell lines [Chinese hamster ovary (CHO), Chinese hamster lung V79, and mouse lymphoma cells [Paschin et al, 1983;McGregor et al, 1987]. Clastogenic activity is induced in cultured CHO cells [Seoane and Dulout, 1999], mouse mammary FM3A carcinoma cells [Umeda and Nishmura, 1979] and human lymphocytes [Nakamuro et al, 1978;Sarto et al, 1980;Stella et al, 1982].…”

Responses of the L5178Y mouse lymphoma forward mutation assay: V. Gases and vapors

“…Failure to detect small colonies could lead to errors in the conclusions since predominantly small-colony inducing compounds may be judged as non-mutagenic. During this project, which has involved the testing of many compounds [see McGregor et al, 1987;1988a,b], these additional measurements were not routinely made because it was believed that the demonstration of any clastogenic effects would be less ambiguous by metaphase analysis in the appropriate experiments; the objective was to demonstrate whether there was a mutagenic effect detectable by the assay. Furthermore, it has not been shown conclusively that small colonies are necessarily indicative of clastogenic events [Blazak et al, 19891.…”