Modification of the umu-assay (ISO 13829) accounting for cytotoxicity in genotoxicity assessment: A preliminary study
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In: Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol. 747, No. 2, 18.09.2012, p. 190-196.
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TY - JOUR
T1 - Modification of the umu-assay (ISO 13829) accounting for cytotoxicity in genotoxicity assessment: A preliminary study
AU - Toolaram, Anju Priya
AU - Gutiérrez, Iris Raquel
AU - Ahlf, Wolfgang
PY - 2012/9/18
Y1 - 2012/9/18
N2 - In this study, the umu-assay (ISO 13829) was modified by addition of the resazurin-reduction assay to assess the cytotoxic potential of toxins. The aim was to develop a test system that was capable of examining both genotoxicity and cytotoxicity on the basis of the metabolic health of the cells so as to provide a better assessment of the negative influence of toxic effects on the evaluation of genotoxicity. The test was established and validated with mitomycin C (MMC), 1,3-dinitropyrene (1,3-DNP), 4-nitroquinoline-1-oxide (4-NQO) and chloramphenicol (CHL) as toxins with known responses in the umu-assay. The results indicate that the modified umu-assay was able to reveal genotoxic responses towards MMC, 1,3-DNP and 4-NQO up to 1 μg/ml. Further, the assay was able to determine the cytotoxicity of CHL, MMC and 4-NQO. Hence, the modified umu-assay was proven to be a sensitive test for determining the cytotoxicity and genotoxicity of toxins, with results that were comparable with literature data. Moreover, the modified umu-assay showed that cytotoxic concentrations that cause >50% inhibition of dehydrogenase activity (DHA) can result in unreliable computation of genotoxicity.
AB - In this study, the umu-assay (ISO 13829) was modified by addition of the resazurin-reduction assay to assess the cytotoxic potential of toxins. The aim was to develop a test system that was capable of examining both genotoxicity and cytotoxicity on the basis of the metabolic health of the cells so as to provide a better assessment of the negative influence of toxic effects on the evaluation of genotoxicity. The test was established and validated with mitomycin C (MMC), 1,3-dinitropyrene (1,3-DNP), 4-nitroquinoline-1-oxide (4-NQO) and chloramphenicol (CHL) as toxins with known responses in the umu-assay. The results indicate that the modified umu-assay was able to reveal genotoxic responses towards MMC, 1,3-DNP and 4-NQO up to 1 μg/ml. Further, the assay was able to determine the cytotoxicity of CHL, MMC and 4-NQO. Hence, the modified umu-assay was proven to be a sensitive test for determining the cytotoxicity and genotoxicity of toxins, with results that were comparable with literature data. Moreover, the modified umu-assay showed that cytotoxic concentrations that cause >50% inhibition of dehydrogenase activity (DHA) can result in unreliable computation of genotoxicity.
KW - Chemistry
KW - umu-Assay
KW - Cytotoxicity
KW - Genotoxicity
KW - Resazurin-reduction assay
KW - Sustainability Science
UR - http://www.scopus.com/inward/record.url?scp=84863779946&partnerID=8YFLogxK
U2 - 10.1016/j.mrgentox.2012.05.010
DO - 10.1016/j.mrgentox.2012.05.010
M3 - Journal articles
C2 - 22659122
VL - 747
SP - 190
EP - 196
JO - Mutation Research/Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research/Genetic Toxicology and Environmental Mutagenesis
SN - 1383-5718
SN - 1879-3592
IS - 2
ER -