HGPRT locus mutation

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). 

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. 

Paschin YV, Bahitova LM. 1982. Mutagenicity of benzo[a]pyrene and the antioxidant phenol at the HGPRT locus of V79 Chinese hamster cells. Mutat Res 104 389-393. 

Fox, M. Delow, G.F. (1985) Tests for mutagenic activity at the HGPRT locus in Chinese hamster V79 cells in culture. In Ashby, J., de Serres, F.J., Draper, M., Ishidate, M., Jr, Margolin, B.H., Matter, B.E. Shelby, M.D., eds, Progress in Mutation Research, Volume 5, Evaluation of Short-Term Tests for Carcinogens. Report of the International Programme on Chemical Safety s Collaborative Study on in vitro assays, Amsterdam, Elsevier Science, pp. 517-523... 

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. 

Fox, M. Delow. GF. (1985) Tests for mutagenic activity at the HGPRT locus in Chinese hamster V79 cells in culture. Prog. Mutat. Res., 5, 517-523... 

Prenatal and postnatal development rats Genetic toxicology Ames test, chromosomal aberrations in mammalian cells, micronuclei in mice, gene mutation at the HGPRT locus Carcinogenicity none... 

Not genotoxic (Ames, in vitro chromosomal aberrations in mammalian cells, in vivo mouse MN, in vitro gene mutation of HGPRT locus)... 

The cytotoxic, clastogenic and mutagenic effects of HD in Chinese hamster ovary cells have also been evaluated by Jostes et al. (1989). Chromosomal aberration frequency increased in a dose-dependent manner over the dose range of 0.0625 to 0.25 pM. Mutation induction at the HGPRT locus was sporadic, but the majority of the exposures resulted in mutation frequencies that were 1.2 to 4.0 fold higher than the spontaneous frequencies. 

Cytogenetic examination of bone marrow cells showed no increase in aberrations in maternal and neonatal rats following maternal oral exposure to a DeBDE and NoBDE mixture. In vitro assays found that DeBDE did not induce gene mutations in several bacterial tests (Ames assays) or in mammalian cells. DeBDE also did not induce chromosomal aberrations in Chinese hamster ovary cells. However, exposure to the congeners 2,2, 4,4 -tetra-BDE, 3,4-diBDE, and 2-monoBDE caused increased recombinogenic activity at the HGPRT locus in several cell lines. 

CR is stated not to be genotoxic in a Salmonella bacterial mutagenicity test, a CHO forward gene mutation test (HGPRT locus), mouse lymphoma cell assay (L5178Y/tk+/tk ), and a micronucleus test (Colgrave et al, 1983). 

V79 Chinese hamster lung HGPRT locus, forward mutation 6-TGr 2, 43, 39... 

Paschin YV, Kozachenko VL, Sal nikova LE (1983) Differential mutagenic response at the HGPRT locus in V-79 and CHO cells after treatment with chromate. Mutat Res 122 362-365 Patterson RR, Fendorf S, Fendorf M (1997) Reduction of hexavalent chromium by amorphous iron sulfide. Environ Sci Technol 31 2039-2044... 

However, under these conditions SAB does not increase the frequency of gene mutations at the HGPRT locus (Table 1). 

The long-term rat liver epithelial lines are used for mutagenesis studies because of the need for cell proliferation in such studies. The mutation that has been studied is in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus. This locus is on the X chromosome, and therefore only one... 

J. P. O Neill, P. A. Brimer, R. Machanoff, G. P. Hirsch, and A. W. Hsie, A quantitative assay of mutation induction at the HGPRT locus in Chinese hamster ovary cells (CHO/ HGPRT system) Development and definition of the system, Mutat. Res. 45, 91-101 (1977). 

Comparison of Mutation at the hgprt Locus in Different Human... 

One may compare mutation at the tk locus (FsTdR resistance), at the hgprt locus (6TG resistance), and at the Na /K ATPase locus (OU resistance) via the data in Table 2. While the number of experiments performed to date is small, the mutagens are diverse. In each experiment, mutation for all three markers was measured in the same mutagenized population. 

J. G. DeLuca, J. Krolewski, T. R. Skopek, D. A. Kaden, and W. G. Thilly, 9-Amino-acridine—A frameshift mutagen for Salmonella typhimurium TA 1537 inactive at the hgprt locus in human lymphoblasts, Mutat. Res. 42, 327 (1977). 

We describe in this chapter our experience with the X-linked HGPRT locus and compare some of the results derived from studies with this locus to those obtained with the newly developed thymidine kinase locus, which we believe to be autosomal. Details of the methodology are described, and an attempt is made to compare the utility ofL5178Y cells to that of other cell lines used for specific-locus mutational assays. 

Clearly, further efforts to exploit the use of azg as a selective agent seemed unjustified. It was therefore decided to test 6-mercaptopurine (6-MP), since this substance is also known to undergo ribose phosphorylation through the action of HGPRT enzyme. After several dose-response experiments and some consternation, a standard concentration of 50 ig/ml of 6-MP was deemed suitable. As indicated by the data presented in Table 3, the coincidence survival which troubled us when azg was employed was not a problem. We then proceeded to investigate the efficacy of 6-MP as a selective agent in a forward mutational assay system at the HGPRT locus. 

We have tried to indicate the utility of the thymidine kinase locus in mouse lymphoma cells and the advantages it holds over the more widely employed HGPRT locus. As indicated in this chapter, the amount of labor involved for the utilization of the TK locus is approximately one-tenth that for its X-linked counterpart. This advantage can be exploited to delineate slight increases in the mutation rate above the spontaneous... 

Several mammalian cell systems have been developed in order to determine the potential of food additives and other environmental chemicals to cause gene locus mutations. Some employ rodent cells, as described by Clive and Spector , whereas others use diploid human lymphoblasts as indicator organisms The human lymphoblast system measures the response of hypoxanthine guanine phosphoribosyl transferase (hgprt). Considerable care must be used with these systems for example, the importance of phenotypic lag has been clearly demonstrated by Penman and Thilly. ... 

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