Induced mutations in M13mp2 phage DNA exposed to N-nitrosopyrrolidine with UVA irradiation

Sakae Arimoto-Kobayashi, Naomi Inada, Nobuko Anma, Hiromi Shimada, Hikoya Hayatsu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

It is known that N-nitrosopyrrolidine (NPYR), a carcinogen in rodents, is metabolically activated by microsomal cytochrome P450 to form an α- hydroxylated derivative, which induces mutations. The mutations have been demonstrated by use of Salmonella typhimurium and Escherichia coli. We discovered directly acting mutagenicity of NPYR plus ultraviolet light-A (UVA) in bacteria and phage. With an O6-alkyltransferase-deficient strain of S. typhimurium, the NPYR plus UVA treatment gave greater mutation frequencies compared to those found with the parent strain. We identified the structure of the direct-acting mutagen as N-nitroso-1-phosphonooxypyrrolidine, and analyzed the spectrum of mutations induced in the DNA of M13mp2 phage. The basepair substitutions GC to TA and GC to AT appear to occur predominantly. Several hotspots were observed. In the conditions where SOS response was induced in the host E. coli, greater varieties of mutations were observed in phage DNA compared to those without the SOS response induction. These results suggest that alkylations of DNA occur by the photoactivated NPYR. The roles of the produced damage to the mutations are discussed.

Original languageEnglish
Pages (from-to)24-29
Number of pages6
JournalEnvironmental and Molecular Mutagenesis
Volume34
Issue number1
DOIs
Publication statusPublished - Sep 15 1999

Keywords

  • Mutagenesis
  • Mutation spectrum
  • N- nitrosopyrrolidine
  • Photoactivation
  • UVA
  • Ultraviolet irradiation

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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