Mutation spectrum of 4-nitroquinoline N-oxide in the lacI transgenic Big Blue Rat2 cell line.
This paper describes the spectrum of mutations induced by 4-nitroquinoline N-oxide (4-NQO) in the lacI target gene of the transgenic Big Blue Rat2 cell line. There are only a few report for the mutational spectrum of 4-NQO in a mammalian system although its biological and genetic effects have been well studied. Big Blue Rat2 cells were treated with 0.03125, 0.0625 or 0.125 microg/ml of 4-NQO, the highest concentration giving 85% survival. Our results indicated that the mutant frequency (MF) induced by 4-NQO was dose-dependent with increases from three- to seven-fold. The DNA sequence analysis of lacI mutants from the control and 4-NQO treatment groups revealed an obvious difference in the spectra of mutations. In spontaneous mutants, transition (60%) mutations, especially G:C-->A:T transition (45%), were most frequent. However, the major type of base substitution after treatment of 4-NQO was transversions (68.8%), especially G:C-->T:A (43.8%), while only 25% of mutants were transitions. These results are consistent with those produced by 4-NQO in other systems and the transgenic assay system will be a powerful tool to postulate more accurately the mechanism of chemical carcinogenesis involved.
Ryu
J
J
Toxicology Laboratory, Korea Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul, South Korea. ryujc@kist.re.kr
Youn
J
J
Kim
Y
Y
Kwon
O
O
Song
Y
Y
Kim
H
H
Cho
K
K
Chang
I
I
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins; D016368:Frameshift Mutation; D056968:Lac Repressors; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D017354:Point Mutation; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D056968:Lac Repressors; D009153:Mutagens; D012097:Repressor Proteins; D015112:4-Nitroquinoline-1-oxide; D004247:DNA