In vivo Micronucleus Database
OASIS micronucleus (MN) database was created and is maintained by LMC [1, 2].
Chemicals are defined with CAS, Name, SMILES and observed MN data. The compromised quality of these data is attributed to the fact that many chemicals had been evaluated in the early 1980s; when species (rat vs. mouse) and gender (male vs. female) differences may not always have been considered, etc. To date, the validity of the in vivo MN data has only been verified for chemicals where the in vitro mutagenicity outcome appeared to be negative, relative to the in vivo bone marrow, where the genotoxicity result was positive . Expert judgment was relied upon to consider whether there were factors resulting in inconsistent in vitro results as compared with the in vivo situation (e.g., rodent species differences, non-physiological culture conditions, etc.).
The MN database contains in vivo genotoxicity data assessing possibility of 557 chemicals to induce chromosomal breakage (clastogenicity) and chromosome lagging due to dysfunction of mitotic apparatus (aneugenicity) in bone marrow or peripheral blood of rats and mice . The database included almost equal numbers of positive (267 chemicals, i.e., 48%) and negative (290 chemicals, i.e., 52%) MN assignations performed in either bone marrow or peripheral blood. To illustrate the structural diversity of the database, in vivo MN data were profiled against the set of DNA and protein binding alerts available within the OECD Toolbox v2.1. The results reveal that 251 (45%) of the 557 chemicals possess no DNA and/or protein binding alerts. One 129 of the remaining 306 (55%) chemicals have one or more DNA binding alerts, 57 chemicals have a protein binding alert, and 120 chemicals have both DNA and protein binding alerts.
The MN database has been used to derive mechanistic structure activity-based in vivo model taking into account activation and detoxification of chemicals - in vivo micronucleus formation model .
1. K. Mavournin, D. Blakey, M. Cimino, M. Salamone, J. Heddle, The in vivo micronucleus assay in mammahan bone marrow and peripheral blood. A report of the U.S. Environmental Protection Agency Gene-Tox Program, Mutation Research, 239 (1990), pp. 29-80.
2. A. Wakata, Y. Miyamae, S. Sato, T. Suzuki, T. Morita, N. Asano, T. Awogi, K. Kondo, M. Hayashi, Evaluation of the Rat Micronucleus Test with Bone Marrow and Peripheral Blood: Summary of the 9th Collaborative Study by CSGMT/JEMSrMMS, Environmental and Molecular Mutagenesis, 32, (1998), pp. 84-100.
3. W. Schmid, The micronucleus test, Mutat. Res., Vol. 31, (1975), pp. 9-15.
4. O. Mekenyan, P. Petkov, S. Kotov, S. Stoeva, V. Kamenska, S. Dimitrov, M. Honma, M. Hayashi, R. Benigni, M. Donner, G. Patlewicz, Investigating the Relationship between in Vitro−in Vivo Genotoxicity: Derivation of Mechanistic QSAR Models for in vivo liver genotoxicity and in vivo bone marrow micronucleus formation which encompass metabolism, Chemical Research in Toxicology, Vol. 25, (2012), pp. 277- 296.