CHO/HGPRT mutagenicity assay. II. Genetic basis of 6-thioguanine resistance
An essential aspect of any attempt to study mutation induction in mammalian cells is the demonstration that genetic alterations are the bases for the altered phenotypes. We have defined reproducible conditions for the selection of 6-thioguanine-resistant (TG/sup r) variants of Chinese hamster ovary (CHO) cells. It is known that many such variants contain altered forms of the enzyme hypoxanthine (Hx)-guanine phosphoribosyl transferase (HGPRT). Our question was whether every variant colony which develops under our conditions has properties consistent with a genetic alteration at the HGPRT locus. We considered other possible mechanisms for the TG resistance such as: (a) colony formation by wild-type cells which have escaped the toxic effects of TG as a result of the death of cells and release of purine bases and metabolites into the medium and/or as the result of depletion of medium TG due to inherent decay and cellular metabolism leading to a loss of selection stringency; (b) phenotypic resistance due to some transient, adaptive response in cellular physiology, such as increased rates of purine biosynthesis; (c) stable resistance as a result of mutations at other loci, such as alterations in TG uptake or alterations which affect intracellular levels of purine nucleotides or PRPP. Our conclusion from these studies is that the TG/sup r/ phenotype which is quantified by use of the CHO/HGPRT system does represent genetic alterations, and that we are performing quantitative mutagenesis is determinations with this system. (PCS)
- Research Organization:
- Oak Ridge National Lab., TN (USA)
- Sponsoring Organization:
- Not Available; USDOE
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 6031479
- Report Number(s):
- CONF-790537-3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560301 -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL VARIABILITY
GENETIC VARIABILITY
HAMSTERS
MAMMALS
MUTAGEN SCREENING
MUTAGENESIS
OPTIMIZATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RODENTS
SCREENING
VERTEBRATES