Human micronucleus project

International database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei

Stefano Bonassi, Michael Fenech, Cecilia Lando, Yi ping Lin, Marcello Ceppi, Wushou Peter Chang, Nina Holland, Micheline Kirsch-Volders, E. Zeiger, Sadayuki Ban, Roberto Barale, Maria Paola Bigatti, Claudia Bolognesi, Cao Jia, Marina Di Giorgio, Lynnette R. Ferguson, Aleksandra Fucic, Omar Garcia Lima, P. Hrelia, Ayyathan P. Krishnaja & 12 others Tung Kwang Lee, Lucia Migliore, Ludmilla Mikhalevich, Ekaterina Mirkova, Pasquale Mosesso, Wolfgang Ulrich Müller, Youichi Odagiri, Maria Rosaria Scarffi, Elena Szabova, Irena Vorobtsova, Anne Vral, Andrea Zijno

Research output: Contribution to journalArticle

321 Citations (Scopus)

Abstract

Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5‰ and the interquartile range was between 3 and 12‰. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher level of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods.

Original languageEnglish
Pages (from-to)31-45
Number of pages15
JournalEnvironmental and Molecular Mutagenesis
Volume37
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Micronucleus Tests
Cytokinesis
Lymphocytes
Assays
assay
Databases
Reference Values
laboratory method
historical record
Cytochalasin B
confidence interval
Chromosomes
serum
chromosome
gender
blood
Culture Media
effect
laboratory
comparison

Keywords

  • Biomarkers
  • Cytokinesis-block micronucleus assay
  • DNA damage
  • Peripheral blood lymphocytes
  • Pooled reanalysis

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Human micronucleus project : International database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei. / Bonassi, Stefano; Fenech, Michael; Lando, Cecilia; Lin, Yi ping; Ceppi, Marcello; Peter Chang, Wushou; Holland, Nina; Kirsch-Volders, Micheline; Zeiger, E.; Ban, Sadayuki; Barale, Roberto; Bigatti, Maria Paola; Bolognesi, Claudia; Jia, Cao; Di Giorgio, Marina; Ferguson, Lynnette R.; Fucic, Aleksandra; Lima, Omar Garcia; Hrelia, P.; Krishnaja, Ayyathan P.; Lee, Tung Kwang; Migliore, Lucia; Mikhalevich, Ludmilla; Mirkova, Ekaterina; Mosesso, Pasquale; Müller, Wolfgang Ulrich; Odagiri, Youichi; Scarffi, Maria Rosaria; Szabova, Elena; Vorobtsova, Irena; Vral, Anne; Zijno, Andrea.

In: Environmental and Molecular Mutagenesis, Vol. 37, No. 1, 2001, p. 31-45.

Research output: Contribution to journalArticle

Bonassi, S, Fenech, M, Lando, C, Lin, YP, Ceppi, M, Peter Chang, W, Holland, N, Kirsch-Volders, M, Zeiger, E, Ban, S, Barale, R, Bigatti, MP, Bolognesi, C, Jia, C, Di Giorgio, M, Ferguson, LR, Fucic, A, Lima, OG, Hrelia, P, Krishnaja, AP, Lee, TK, Migliore, L, Mikhalevich, L, Mirkova, E, Mosesso, P, Müller, WU, Odagiri, Y, Scarffi, MR, Szabova, E, Vorobtsova, I, Vral, A & Zijno, A 2001, 'Human micronucleus project: International database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei', Environmental and Molecular Mutagenesis, vol. 37, no. 1, pp. 31-45. https://doi.org/10.1002/1098-2280(2001)37:1<31::AID-EM1004>3.0.CO;2-P
Bonassi, Stefano ; Fenech, Michael ; Lando, Cecilia ; Lin, Yi ping ; Ceppi, Marcello ; Peter Chang, Wushou ; Holland, Nina ; Kirsch-Volders, Micheline ; Zeiger, E. ; Ban, Sadayuki ; Barale, Roberto ; Bigatti, Maria Paola ; Bolognesi, Claudia ; Jia, Cao ; Di Giorgio, Marina ; Ferguson, Lynnette R. ; Fucic, Aleksandra ; Lima, Omar Garcia ; Hrelia, P. ; Krishnaja, Ayyathan P. ; Lee, Tung Kwang ; Migliore, Lucia ; Mikhalevich, Ludmilla ; Mirkova, Ekaterina ; Mosesso, Pasquale ; Müller, Wolfgang Ulrich ; Odagiri, Youichi ; Scarffi, Maria Rosaria ; Szabova, Elena ; Vorobtsova, Irena ; Vral, Anne ; Zijno, Andrea. / Human micronucleus project : International database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei. In: Environmental and Molecular Mutagenesis. 2001 ; Vol. 37, No. 1. pp. 31-45.
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abstract = "Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of {"}normal{"} values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5‰ and the interquartile range was between 3 and 12‰. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19{\%} higher level of MNC frequency (95{\%} confidence interval: 14-24{\%}). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75{\%} of the total variance, with the largest contribution attributable to laboratory methods.",
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AU - Bonassi, Stefano

AU - Fenech, Michael

AU - Lando, Cecilia

AU - Lin, Yi ping

AU - Ceppi, Marcello

AU - Peter Chang, Wushou

AU - Holland, Nina

AU - Kirsch-Volders, Micheline

AU - Zeiger, E.

AU - Ban, Sadayuki

AU - Barale, Roberto

AU - Bigatti, Maria Paola

AU - Bolognesi, Claudia

AU - Jia, Cao

AU - Di Giorgio, Marina

AU - Ferguson, Lynnette R.

AU - Fucic, Aleksandra

AU - Lima, Omar Garcia

AU - Hrelia, P.

AU - Krishnaja, Ayyathan P.

AU - Lee, Tung Kwang

AU - Migliore, Lucia

AU - Mikhalevich, Ludmilla

AU - Mirkova, Ekaterina

AU - Mosesso, Pasquale

AU - Müller, Wolfgang Ulrich

AU - Odagiri, Youichi

AU - Scarffi, Maria Rosaria

AU - Szabova, Elena

AU - Vorobtsova, Irena

AU - Vral, Anne

AU - Zijno, Andrea

PY - 2001

Y1 - 2001

N2 - Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5‰ and the interquartile range was between 3 and 12‰. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher level of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods.

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KW - Cytokinesis-block micronucleus assay

KW - DNA damage

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KW - Pooled reanalysis

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