A CHO mutant, UV40, that is sensitive to diverse mutagens and represents a new complementation group of mitomycin C sensitivity

David B. Busch, Małgorzata Z. Zdzienicka, Adayapalam T. Natarajan, Nigel J. Jones, Wilhemina J I Overkamp, Andrew Collins, David L. Mitchell, Miria Stefanini, Elena Botta, Roberta Bliss Albert, Nan Liu, Deborah A. White, Alain J. Van Gool, Larry H. Thompson

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

A new mitomycin C (MMC)-sensitive rodent line, UV40, has been identified in the collection of ultraviolet light- (UV-) sensitive mutants of Chinese hamster ovary (CHO) cells isolated at the previous Facility for Automated Experiments in Cell Biology (FAECB). It was isolated from an UV mutant hunt using mutagenesis of AA8 cells with the DNA intercalating frameshift mutagen ICR170. It is complemented by CHO-UV-1, irs1, irs3, irs1SF, MC5, V-C8 and V-H4 with respect to its MMC sensitivity based on cell survival, Despite having approx. 4 x normal UV sensitivity and increased sensitivity to UV inhibition of DNA replication, it has near-normal incision kinetics of UV irradiated DNA, and normal (6-4) photoproducts removal. It also is not hypermutable by UV, and shows near normal levels of UV inhibition of RNA synthesis. UV40 also has approx. 11 x, 10 x, 5 x and 2 x AA8 sensitivity to MMC, ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), and X-rays, respectively. Thus, its defect apparently does not involve nucleotide excision repair but rather another process, possibly in replicating past lesions. The spontaneous chromosomal aberration frequency is elevated to 20% in UV40, and the baseline frequency of sister chromatid exchange is also ~ 4-fold increased. The phenotype of UV40 appears to differ from all other rodent mutants that have so far been described.

Original languageEnglish (US)
Pages (from-to)209-221
Number of pages13
JournalMutation Research - DNA Repair
Volume363
Issue number3
DOIs
StatePublished - Aug 8 1996
Externally publishedYes

Keywords

  • DNA repair
  • Fanconi's anemia
  • Mitomycin C
  • Mutants
  • Rodent
  • Ultraviolet light

ASJC Scopus subject areas

  • Toxicology
  • Genetics
  • Molecular Biology

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