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Mutagenesis Advance Access originally published online on September 23, 2006
Mutagenesis 2006 21(6):369-374; doi:10.1093/mutage/gel042
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© The Author 2006. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Nitrocompound activation by cell-free extracts of nitroreductase-proficient Salmonella typhimurium strains

S.G. Salamanca-Pinzón, R. Camacho-Carranza, S.L. Hernández-Ojeda and J.J. Espinosa-Aguirre*

Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México. México

A characterization of nitrocompounds activation by cell-free extracts (CFE) of wild-type (AB+), SnrA deficient (B+), Cnr deficient (A+) and SnrA/Cnr deficient (AB–) Salmonella typhimurium strains has been done. The Ames mutagenicity test (S. typhimurium his+ reversion assay) was used, as well as nitroreductase (NR) activity determinations where the decrease in absorbance generated by nitrofurantoin (NFN) reduction and NADP(H) oxidation in the presence of NFN, nitrofurazone (NFZ), metronidazole (MTZ) and 4-nitroquinoline-1-oxide (4NQO) were followed. Different aromatic and heterocyclic compounds were tested for mutagenic activation: 2-nitrofluorene (2-NF); 2,7-dinitrofluorene (2,7-DNF); 1-nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP); 1,6-dinitropyrene (1,6-DNP); and 1,8-dinitropyrene (1,8-DNP). Differential mutagenicity was found with individual cell free extracts, being higher when the wild type or Cnr containing extract was used; nevertheless, depending on the nitrocompound, activation was found when either NR, SnrA or Cnr, were present. In addition, all nitrocompounds were more mutagenic after metabolic activation by CFE of NR proficient strains, although AB– extract still showed activation capacity. On the other hand, NR activity was predominantly catalyzed by wild type CFE followed by A+, B+ and AB– extracts in that order. We can conclude that results from the Ames test indicate that Cnr is the major NR, while NFN and NFZ reductions were predominantly catalyzed by SnrA. The characterization of the residual NR activity detected by the mutagenicity assay and the biochemical determinations in the AB– CFE needs further investigation.

*To whom correspondence should be addressed. Tel: +52 56229214; Fax: +52 56229182; Email: jjea{at}servidor.unam.mx


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