Persistently elevated frequency of spontaneous mutations in progeny of CHO clones surviving X-irradiation: association with delayed reproductive death phenotype

Wushou P. Chang, John B. Little

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Certain clonal progeny of Chinese hamster ovary (CHO) cells surviving X-irradiation demonstrate pleomorphic changes including a persistently decreased cloning efficiency, a dominant phenotype we have termed delayed reproductive death (Chang and Little, 1991, 1992b). We now report that cells from these progeny clones show a persistently elevated frequency of spontaneous mutations at the hprt locus for up to 95-100 population doubling post-irradiation. Mutant fractions as high as 10-3 were scored, more than two orders of magnitude higher than those observed in clonal progeny of non-irradiated cells studied in parallel. These results are discussed in terms of the hypothesis that radiation induces a type of genetic instability among some surviving cells that results in a heritable mutator phenotype, and that this instability may also be involved in the phenomenon of delayed reproductive death.

Original languageEnglish
Pages (from-to)191-199
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume270
Issue number2
DOIs
Publication statusPublished - Nov 16 1992
Externally publishedYes

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Mutation Rate
Cricetulus
Ovary
Clone Cells
Phenotype
Organism Cloning
Radiation
Population

Keywords

  • Chinese hamster ovary (CHO) cells
  • Delayed reproductive death
  • Hprt
  • Mutator
  • X-Irradiation

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis

Cite this

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AU - Little, John B.

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N2 - Certain clonal progeny of Chinese hamster ovary (CHO) cells surviving X-irradiation demonstrate pleomorphic changes including a persistently decreased cloning efficiency, a dominant phenotype we have termed delayed reproductive death (Chang and Little, 1991, 1992b). We now report that cells from these progeny clones show a persistently elevated frequency of spontaneous mutations at the hprt locus for up to 95-100 population doubling post-irradiation. Mutant fractions as high as 10-3 were scored, more than two orders of magnitude higher than those observed in clonal progeny of non-irradiated cells studied in parallel. These results are discussed in terms of the hypothesis that radiation induces a type of genetic instability among some surviving cells that results in a heritable mutator phenotype, and that this instability may also be involved in the phenomenon of delayed reproductive death.

AB - Certain clonal progeny of Chinese hamster ovary (CHO) cells surviving X-irradiation demonstrate pleomorphic changes including a persistently decreased cloning efficiency, a dominant phenotype we have termed delayed reproductive death (Chang and Little, 1991, 1992b). We now report that cells from these progeny clones show a persistently elevated frequency of spontaneous mutations at the hprt locus for up to 95-100 population doubling post-irradiation. Mutant fractions as high as 10-3 were scored, more than two orders of magnitude higher than those observed in clonal progeny of non-irradiated cells studied in parallel. These results are discussed in terms of the hypothesis that radiation induces a type of genetic instability among some surviving cells that results in a heritable mutator phenotype, and that this instability may also be involved in the phenomenon of delayed reproductive death.

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