Detection of oxidative mutagenesis by isoniazid and other hydrazine derivatives in Escherichia coli WP2 tester strain IC203, deficient in OxyR: strong protective effects of rat liver S9.
Strain IC203, deficient in the OxyR function, was sensitive to both cytotoxic and mutagenic effects of isoniazid (INH) whereas its parent, WP2 uvrA/pKM101, was resistant to these effects. Four other hydrazine compounds, hydrazine hydrate (HZH), phenylhydrazine (PHZ), hydralazine (HLZ) and nialamide (NLD), were mutagenic in WP2 uvrA/pKM101. Increases in mutagenicity were observed in IC203 for HZH and PHZ but not for HLZ and NLD. Growth inhibition zones by HZH, PHZ and NLD were larger in IC203 than in WP2 uvrA/pKM101. The enhancements in the effects of INH, HZH and PHZ in IC203 with respect to its oxyR+ parent are considered to be caused by the production of reactive oxygen species. This is consistent with its inhibition in IC203 by S9 from liver of uninduced rats, probably through the action of catalase. Mutagenicities of INH, PHZ and HLZ were low in strains IC204, a derivative of WP2 uvrA carrying a deletion of the umuDC genes, and IC206, a derivative of IC204 deficient in the MutY glycosylase. In these strains, HZH and NLD induced a high level of revertants which carry suppressor mutations resulting exclusively from G:C-A:T transitions, thus suggesting a direct reaction of the two hydrazines with cytosine.
Blanco
M
M
Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomédicas, Amadeo de Saboya 4, 46010 Valencia, Spain.blanco@ochoa.fib.es
Martínez
A
A
Urios
A
A
Herrera
G
G
O'Connor
J E
JE
D000818:Animals; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects*; D029968:Escherichia coli Proteins; D007538:Isoniazid / Q000031:analogs & derivatives / Q000633:toxicity*; D008099:Liver / Q000502:physiology; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010084:Oxidation-Reduction; D051381:Rats; D017382:Reactive Oxygen Species / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D013045:Species Specificity; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D009153:Mutagens; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D014157:Transcription Factors; C499299:oxyR protein, E coli; D007538:Isoniazid