title: HUMN project initiative and review of validation, quality control and prospects for further development of automated micronucleus assays using image cytometry systems.
abstract: The use of micronucleus (MN) assays in in vitro genetic toxicology testing, radiation biodosimetry and population biomonitoring to study the genotoxic impacts of environment gene-interactions has steadily increased over the past two decades. As a consequence there has been a strong interest in developing automated systems to score micronuclei, a biomarker of chromosome breakage or loss, in mammalian and human cells. This paper summarises the outcomes of a workshop on this topic, organised by the HUMN project, at the 6th International Conference on Environmental Mutagenesis in Human Populations at Doha, Qatar, 2012. The aim of this paper is to summarise the outcomes of the workshop with respect to the set objectives which were: (i) Review current developments in automation of micronucleus assays by image cytometry; (ii) define the performance characteristics of automated MN scoring using image cytometry and methods of assessment for instrument validation and quality control and (iii) discuss the design of inter-laboratory comparisons and standardisation of micronucleus assays using automated image cytometry systems. It is evident that automated scoring of micronuclei by automated image cytometry using different commercially available platforms [e.g. Metafer (MetaSystems), Pathfinder™ (IMSTAR), iCyte(®) (Compucyte)], particularly for lymphocytes, is at a mature stage of development with good agreement between visual and automated scoring across systems (correlation factors ranging from 0.58 to 0.99). However, a standardised system of validation and calibration is required to enable more reliable comparison of data across laboratories and across platforms. This review identifies recent progress, important limitations and steps that need to be taken into account to enable the successful universal implementation of automated micronucleus assays by image cytometry.
authors.affiliation: CSIRO Preventative Health Flagship, PO Box 10041 Adelaide BC, 5000, Australia. michael.fenech@csiro.au
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
authors.forename: Micheline
authors.initials: M
authors.lastname: Kirsch-Volders
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossnerova
authors.forename: Radim
authors.initials: R
authors.lastname: Sram
authors.forename: Horst
authors.initials: H
authors.lastname: Romm
authors.forename: Claudia
authors.initials: C
authors.lastname: Bolognesi
authors.forename: Adarsh
authors.initials: A
authors.lastname: Ramakumar
authors.forename: Francoise
authors.initials: F
authors.lastname: Soussaline
authors.forename: Christian
authors.initials: C
authors.lastname: Schunck
authors.forename: Azeddine
authors.initials: A
authors.lastname: Elhajouji
authors.forename: Wagida
authors.initials: W
authors.lastname: Anwar
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
mesh_terms: D000818:Animals; D057205:Automation, Laboratory; D006801:Humans; D019044:Image Cytometry / Q000295:instrumentation*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity; D011786:Quality Control; D015203:Reproducibility of Results
chemical_list: D009153:Mutagens
keywords: Automation; Cytokinesis-block; Image cytometry; Lymphocytes; Micronucleus