Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phenotypic instability of a 8-azaguanine (AG)-resistant clone A14--2c-1 was previously reported (Abramyan et al., 1979) to be determined by genetic (replicative) instability. Further, phenotype gene activity changes are characteristic of genetically instable "mutant", which may be "passed" from one locus to another. In the present work, some clones were isolated from clone A14-2c-1 differing in their sensitivity to lethal UV-radiation, lethal dose D37 differences being almost 6 times. During a further cultivation through 90 passages (300 cell generations), two of four clones changed their D37 values: for clone 2c-15 it increased by 3 times, for clone 2c-16 it decreased more than twice. Besides, subclones of 2c-15 and 2c-16 clones had also different D37 values. With respect to AG-resistance, clone 2s-15 was shown to have LD50 to AG, similar to that of the parental one-while in 3 other clones LD50 was 3 times as much. These differences are associated with variations in hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity: in clones A14-2c-1 and 2c-15 this activity is two times higher than in other clones. All the clones have the same value of the Michaelis constant for hypoxanthine and phosphoribosylpyrophosphate. It can be outlined that difference in HPRT activity and quantity in cells are closely related. Thus, phenotypic instability of A14-2c-1 clone offers characteristic features of genetic (replicative) instability: instability in AG-resistance and UV-sensitivity coincides with interclonal heterogeneity according to unstable markers; the unstable property may be transmitted from one locus (responsible for AG-resistance) to be another one (UV-sensitivity); and different level of AG-resistance in clones is probably determined by changes in gene activity, which lead to differences in HPRT quantity in cells.
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PMID:[Intraclonal heterogeneity and instability of CHO-K1 Chinese hamster cells in sensitivity to ultraviolet light and resistance to 8-azaguanine]. 729 4