Open AccessLack of Direct Involvement of 8‐Hydroxy‐2′‐deoxyguanosine in Hypoxanthine‐guanine Phosphoribosyltransferase Mutagenesis in V79 Cells Treated with N,N'‐Bis(2‐hydroxyperoxy‐2‐methoxyethyl)‐l,4,5,8‐naphthalenetetracarboxylic‐diimide (NP‐III) or Riboflavin
Author(s) -
Nakajima Madoka,
Takeuchi Toru,
Ogino Keiki,
Morimoto Kanehisa
Publication year - 2002
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2002.tb02165.x
Subject(s) - hypoxanthine guanine phosphoribosyltransferase , mutant , mutagenesis , transversion , deoxyguanosine , microbiology and biotechnology , guanine , phosphoribosyltransferase , mutation , biology , biochemistry , dna , chemistry , gene , nucleotide
The object of this study is to investigate the relationship between a typical product of oxidative DNA damage, 8‐hydroxy‐2′‐deoxyguanosine (8OHdG), and mutagenesis in V79 cells through a molecular analysis of hypoxanthine‐guanine phosphoribosyltransferase ( hprt ) gene mutants. We performed a direct sequencing analysis of the cDNA of mutants obtained after treatment with N,N'‐bis(2‐hydroxyperoxy‐2‐methoxyethyl)‐l,4,5,8‐naphthalenetetracarboxylic‐diimide (NP‐III) or riboflavin, each of which induces the formation of 8OHdG in cellular DNA upon UVA irradiation. The frequency of mutation after both treatments was no more than 2 to 5 times the control value. A considerable number of the mutants could not be amplified by RT‐PCR, and this was also the case for the control mutants. Among the mutants analyzed, deletions and a TA→Ã transversion occurred predominantly. The reasons for the weak association of induction of 8OHdG with frequency of mutation and the possible mechanism of oxidative‐stress‐derived mutagenesis are discussed.