HGPRT systems

Chinese Hamster CHO/Hgprt System. Chinese hamster ovary (CHO) cells have 21 or 22 chromosomes with one intact X chromosome and a large acrocentric marker chromosome (Natarajan and Obe, 1982). The use of these cells in mammalian mutation experiments was first reported by Hsie et al. (1975), and was refined into a quantitative assay for mutagenicity testing by O Neill. The performance of this system has been reviewed by the USA EPA Gene-Tox Program. The experimental procedure for this assay is similar to the V79/Hgprt system already described, and for more detailed descriptions the reader is referred to Li et al. (1987). 

Brimer PA, Tan EL, Hsie AW. 1982. Effect of metabolic activation on the mutagenicity and cytotoxicity of ethylene dibromide in the CHO/HGPRT system. Mutat Res 95 377-388. 

Irr, J.D. and Snee, R.D. (1979). Statistical evaluation of mutagenicity in the CHO/HGPRT system, page 263 in Banbury Report 2, Mammalian Cell Mutagenesis The Maturation of Tkst Systems. Hsie, A.W., 0 Neil, J.P., AND McElheny, V.K., Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York). 

Thielmann, H.W., Schroder, C.H., O Neill, J.P., Brimer, P.A., and Hsie, A.W. (1979). Relationship between DNA alkylation and specific-locus mutation induced by N-methyl- and N-ethyl-N-nitrosourea in cultured Chinese hamster ovary cells (CHO/HGPRT system), Chem. BioL Interact 26,233. 

Hsie, A.W., O Neill, J.P., Machanoff, R., Schenley, R.L. Brimer, PA. (1981) Screening for mutagenic response of four coded chemicals by the CHO/HGPRT system. In de Serres, F.J. Ashby, J., eds. Evaluation of Short-Term Tests for Carcinogens. Report of the International Collaborative Program (Progress in Mutation Research, Vol. 1). Amsterdam, Elsevier, pp.602-607... 

Mutation Chinese hamster V79 lung cells HGPRT system... 

Hirsch, and A.W. Hsie. A quantitative assay of mutation induction at hypoxanthine-guanine phospho-ribosyl transferase locus in Chinese hamster ovary cells (CHO/HGPRT system) Development and definition of the system. Mutat. Res. 45 91-101, 1977. 

Neill JP, Machanoff R, San Sebastian JR, et al. 1982. Cytotoxicity and mutagenicity of dimethylnitrosamine in mammalian cells (CHO/HGPRT system) Enhancement by calcium phosphate. Environ Mutagen 4 7-18. 

Bootman, J., G.Hodson-Walker, and J.M.Lloyd. 1988b. CFC141b Investigation of mutagenic activity at the HGPRT locus in a Chinese hamster V79 cell mutation system. 88/ PSV005/257, Life Science Research Laboratory, EYE, Suffolk, England (Cited in ECETOC 1994). 

Gene mutation in cultured mammalian cells such as Chinese Hamster V79 cell/HGPRT mutation system. 

V79 System. The Chinese hamster V79 line was established in 1958 (Ford and Yerganian, 1958). Publication of the use of the line for mutation studies (by measuring resistance to purine analogues due to mutation of the Hgprt locus) occurred 10 years later (Chu and Mailing, 1968). The V79 line was derived from a male Chinese hamster hence, V79 cells possess only a single X chromosome. 

One system uses mouse lymphoma cells and detects mutations that cause deficiency of thymidine kinase (TK). Another uses Chinese hamster cells and detects mutations in the gene that produces hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Both tests cure efficient, are widely applied, and can be completed in a few weeks. Although not as simple, rapid, and efficient as the Salmonella tests, they have the advantage of being done in a eukaryote. Mammalian-cell cultures cure also used to test for chromosomal mutation. 

For the short-term tests, we recommend a two-tier system. Tier I consists of a microbial gene-mutation test (Salmonella/microsome test), a mammalian cell-culture gene-mutation test (HGPRT or IK), and a mammalian cell-culture chromosomal-breakage test. All these cure to be done both with and without metabolic activation. If the... 

Gene mutation tests in a eukaryotic system in vitro, e.g. the Hypoxanthine - guanine - phosphoribosyl - transferase (HGPRT) gene mutation tests in hamster cells. 

O Neill JP and Hsie AW (1979) The CHO/HGPRT mutation assay experimental procedure. In Hsie AW, O Neill JP, and McElhenny VK (eds.) Mammalian Cell Mutagenesis The Maturation of Test Systems, Banbury Report No. 2, pp. 55-70, 311-318, 407-420. Cold Spring Harbor, NY Cold Spring Harbor Press. 

Complete deficiency of HGPRT results in gout-related arthritis, dramatic malfunction of the nervous system, behavioral disorders, learning disability, and hostile or aggressive behavior, often self directed. In the most extreme cases, patients nibble at their fingertips or, if restrained, their lips, causing severe self-mutilation. 

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