Characterization of the mutational specificity of DNA cross-linking mutagens by the Lac+ reversion assay with Escherichia coli.
The mutational specificities of DNA cross-linking compounds such as cisplatin, transplatin, carboplatin, mitomycin C, psoralen, and 8-methoxypsoralen were investigated in lacZ reversion assay systems of Escherichia coli. Tester strains were constructed by introducing the six kinds of F' plasmids (lacI-, lacZ461, and proAB+), each of which carries a different base-substitution mutation within the lacZ gene. Each of the six possible base-substitution mutations was assayed by Lac+ reversion. Cisplatin induced G.C-->A.T transitions and G.C-->T.A transversions, with the former predominating. Transplatin induced A.T-->G.C transitions in addition to G.C-->A.T transitions and G.C-->T.A. Carboplatin weakly induced G.C-->A.T transitions. On the other hand, mitomycin C induced only G.C-->T.A transversions, while psoralen and 8-methoxypsoralen reactivated with near-UV irradiation induced A.T-->G.C transitions preferentially. The Lac(+) reversion system was very convenient for rapidly determining mutational spectra.
Ohta
T
T
School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan. ohta@ls.toyaku.ac.jp
Ohmae
S
S
Yamaya
K
K
Kanemichi
Y
Y
Tokishita
S
S
Yamagata
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D016190:Carboplatin / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D005363:Ficusin / Q000494:pharmacology; D007763:Lac Operon / Q000187:drug effects* / Q000235:genetics; D008027:Light; D008730:Methoxsalen / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D009154:Mutation; D017319:Photosensitizing Agents / Q000494:pharmacology; D017354:Point Mutation
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D009153:Mutagens; D017319:Photosensitizing Agents; C034697:transplatin; D016685:Mitomycin; D016190:Carboplatin; D005363:Ficusin; D002945:Cisplatin; D008730:Methoxsalen