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Spontaneous genetic instabilities in a chromosomally-located HSV-1 thymidine kinase (TK) gene in a transformed human cell line

Authors
Publisher
McGill University
Publication Date
Keywords
  • Biology
  • Genetics.
  • Biology
  • Microbiology.

Abstract

We have studied spontaneous mutations in a chromosomally-located, single copy HSV-1 thymidine kinase (TK) gene in a human AK 143 TK$ sp-$ cell line. We have used three anti HSV-1 thymidine kinase nucleotide analogues, namely Trifluorothymidine (TFT), Acyclovir (ACV) and DHPG (9-(1,3-dihydroxy-2-propoxy-methyl)guanine), to select for $TK sp-$ mutants. The spontaneous mutation rate for the TK gene was very high in this system. The mutation frequency was 5 $ times$ 10$ sp{-3}$ per cell per generation when Acyclovir (ACV) was used as a selective agent and 5 $ times$ 10$ sp{-4}$ per cell per generation when Trifluorothymidine (TFT) was used. The spontaneous mutation frequency dropped to 1 $ times$ 10$ sp{-5}$ per cell per generation when a combination of TFT plus ACV was used and to 1 $ times$ 10$ sp{-6}$ per cell per generation when a combination of TFT plus DHPG (9-(1,3-dihydroxy-2-propoxy-methyl)guanine) was used as selective agents.

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