Correcting for toxic inhibition in quantification of genotoxic response inthe umuC test

Citation
A. Baun et al., Correcting for toxic inhibition in quantification of genotoxic response inthe umuC test, MUT RES-GTE, 441(2), 1999, pp. 171-180
Citations number
14
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
ISSN journal
13835718 → ACNP
Volume
441
Issue
2
Year of publication
1999
Pages
171 - 180
Database
ISI
SICI code
1383-5718(19990517)441:2<171:CFTIIQ>2.0.ZU;2-C
Abstract
An improved procedure for quantification of results from the umuC tests for genotoxicity is presented. The calculation method better separates toxic g rowth inhibition (cytotoxicity) from genotoxic effects than currently used methods and therefore, greatly extends the applicability of genotoxicity te sts on environmental samples. The basic principle is to normalize the genot oxic response compensating for both decreasing biomass and growth rate redu ction that results from cytotoxicity. The improved method and the currently used method was compared for umuC tests on the pure compounds: methylmetha nesulfonate (MMS), N-methyl-N'-nitro-N-nitroguanidine (MNNG), sodium azide (NaN3), and 4-nitroquinoline-1-oxide (4-NQO). For compounds with no or low cytotoxicity, the two calculation methods gave practically identical result s, while for highly cytotoxic compounds, the traditional method overestimat ed genotoxicity. umuC tests were also carried out on leachate polluted grou ndwater sampled downgradient of a landfill (Grindsted, Denmark). All pollut ed samples showed high cytotoxicity concomitant with high genotoxicity when the results were quantified in the traditional way. The new method showed that these results were in fact false positive, as the apparent genotoxicit y was a result of cytotoxicity. Based on the mathematical analysis leading to the improved procedure for correction for cytotoxicity, it is suggested to alter the present test design of the umuC test in order to obtain well-d efined exposure concentrations as well as mathematical consistency in the q uantification of genotoxicity. (C) 1999 Elsevier Science B.V. All rights re served.