Thioguanine resistance

Garner RC, Campbell J. 1985. Tests for the induction of mutations to ouabain or 6-thioguanine resistance in mouse lymphoma L5178Y cells. In Ashby J, de Serres FJ, et al., eds. Progress in mutation research. Vol. 5. Evaluation of short-terms tests for carcinogens. Amsterdam, The Netherlands Elsevier Science Publishers, 525-529. 

The concentration of toxin which causes a 50% reduction in cell bound dye after five days in culture. Cell lines used were H4TG, thioguanine-resistant rat hepatoma cells MDCK, Madin-Darb and canine kidney cells NIH3T3,NIH Swiss mouse embryo fibroblasts and KA31T, Kirsten strain of Moloney sarcoma virus-transformed 3T3 cells. 

Activation by co-cultivation with X-irradiated primary rat hepatocytes Growth of V79 (T2-14) 6-thioguanine-resistant cells... 

In cultured human lymphocytes, the frequency of mutations for thioguanine resistance increases as a linear nonthreshold function of the x-ray dose over the range from 10 to 100 mGy (1 to 10 rad) (see Figure 7.1) and is essentially the same whether the dose is delivered in several fractionated exposures or in a single brief exposure (Grosovsky and Little, 1985). 

Fig. 7.1 Induction of 6-thioguanine resistance by x rays in TK-6 human diploid lymphoblasts. The line shown, fitted by linear regression analysis, has a sl< of 6.0 0.56 TG" cells per 10 Gy (10 rad) (from Grosovsky and Little, 1985).

Huang, S.L. and Lieberman, M.W. (1978). Induction of 6-thioguanine resistance in human cells treated with N-acetoxy-2-acetylaminofluorene, Mutat. Res. 57,349. 

Jensen, D, and Ramel, C. (1980). Relationship between chemical damage of DNA and mutations in mammalian cells. 1. Dose-response curves for the induction of 6-thioguanine resistant mutants by low doses of monofunctional alkylating agents, x rays and UV radiation in V79 Chinese hamster cells, Mutat. Res. 73,339. 

The frequency of 6-thioguanine-resistant cells has been reported to be about 10 14 among peripheral blood lymphocytes of normal persons. The frequency is generally higher among cancer patients on therapy with known mutagens. 

Maier, P., P. Manser, and G. Zbinden. Granuloma pouch assay. II. Induction of 6-thioguanine resistance by MNNG and benzo(a)pyrene in vivo. Mutat. Res. 

Strauss, G.H., and R.J. Albertini. Enumeration of 6-thioguanine-resistant peripheral blood lymphocytes... 

Kenne K, Ljungquist S, Ringertz NR. 1986. Effects of asbestos fibers on cell division, cell survival, and formation of thioguanine-resistant mutants in Chinese hamster ovary cells. Environ Res 39 448-464. 

Aidoo, A., Lyn-Cook, L. E., Mittelstaedt, R. A., Heflich, R. H., and Casciano, D. A. (1991). Induction of 6-thioguanine-resistant lymphocytes in Fischer 344 rats following in vivo exposure to M-ethyl-iV-nitrosourea and cyclophosphamide. Environ Mol Mutagen 17, 141-151. 

Bookland, E.A., Reznikoff C.A., Lindstrom, M., and Swaminathan, S. (1992) Induction of thioguanine-resist-ant mutations in human uroepithelial cells by 4-aminobiphenyl and its N-hydroxy derivatives. Cancer Res., 52, 1615-1621. 

RDX was shown to be inactive in the UDS in WI-38 human fibroblasts, with and without S9 metabolic activation [47], Reported test concentrations were in the range of 250 to 4000 pg ml-1, well over the aqueous solubility of the compound (approximately 70 pg ml-1) [48], Similarly, in the HGPRT-V79 assay with or without metabolic activation, both RDX and HMX were inefficient in inducing 6-thioguanine resistant cells. The test concentrations used were up to 40 pg ml1 for RDX and 10 pg ml-1 for HMX, close to the solubility limit of these compounds in water [2], Another confirmation of the lack of mutagenic activity of RDX was provided recently when the compound was found inactive in the mouse lymphoma forward mutation assay using the L5178Y cell line [49],... 

Lee TC, Huang RY and Jan KY (1985), Sodium arsenite enhances the cytotoxicity, dastogenicity and 6-thioguanine-resistant mutagenicity of ultraviolet light in Chinese Hamster ovary cells. Mutat. Res. 148 83 -89. 

Cleaver JE (1984) Differential toxicity of 3-aminobenzamide to wild-type and 6-thioguanine-resistant Chinese hamster cells by interference with pathways of purine biosynthesis. Mutat Res 131 123-127... 

Survival and Mutagenesis from Radiation in CHO Cells. 3AB (1 vaM) had no significant effect on cell survival or the yield of 6-thioguanine-resistant mutations after irradiation with X-rays (Tables 1 and 2). Ouabain mutations were not investigated because of the extremely low yield of ouabain-resistant mutants from X-rays [8]. 

AB (1 mAf) subtly increased the toxicity and reduced mutagenesis from UV light. The reduction in Do was approximately 20% (Table 1). The rate of mutagenesis per J m to ouabain or 6-thioguanine resistance was reduced about 30% by 3AB. 

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