Chromosome aberration test bone marrow

Purpose. The purpose of the in vivo chromosome aberration test is to evaluate the potential of the test substance to cause chromosomal aberrations in bone marrow cells of experimental animals (usually rodents) (Tice et al. 1994 Preston et al. 1987). 

Study Design. Bone marrow cells are sampled 1.5 normal cell cycles (12-18 hours) after compound administration, and they are sampled optionally 24 hours later in additional groups of animals. In case of multiple administrations, cells are sampled 1.5 normal ceU cycles (12-18 hours) after the last treatment. In order to accumulate cells in metaphase and make the scoring easier, the animals receive a 

Immediately after sacrifice, bone marrow cells are collected from femurs or tibias, exposed to hypotonic treatment, fixed, spread on slides, and stained. The slides are then scored visually under the microscope. Structural chromosome aberrations should be analyzed in at least 100 metaphase cells per animal. To this end, for each cell, the number and type of aberrations (chromatid or chromosome breaks and gaps, as well as the different types of chromatid and chromosome rearrangements) should be recorded. The incidence of polyploid cells and of cells with endoreduplicated chromosomes should also be reported because they potentially reflect the induction of numerical chromosome aberrations and/or inhibition of cell cycle progression. In addition, the mitotic index, used as a cytotoxicity parameter, is calculated for 1000 cells per animal. With cytotoxic compounds, the highest dose level should induce at least a 50% reduction in the mitotic index (OECD 1997b Richold et al. 1990 Tice et al. 1994). 

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Mammalian Bone Marrow Chromosomal Aberration Test (Updated Guideline, adopted 21 July 1997)... 

Mammalian bone marrow chromosomal aberration test (August 1998)... 

B.ll Mutagenicity - In Vivo Mammalian Bone Marrow Chromosome Aberration Test (20(X))... 

B.ll Mutagenicity - In vivo mammalian bone-marrow chromosome aberration test B.12 Mutagenicity mammalian erythrocyte micronucleus test B.20 Sex-Unked recessive lethal test in Drosophila melanogaster B.22 Rodent dominant lethal test... 

The mammalian in vivo bone marrow chromosome aberration test... 

Positive results in the mammalian in vivo bone marrow chromosome aberration test indicate that a substance induces stmctural chromosome aberrations in the bone marrow of the species tested. An increase in polyploidy (a multiple of the haploid chromosome number (n) other than the diploid number, i.e., 3n, 4n and so on) may indicate that a substance has the potential to induce numerical aberrations (change in the number of chromosomes from the normal number characteristic of the animals utilized). 

OECD Guideline 475 (1997) Mammalian Bone Marrow Chromosome Aberration Test. Adopted July 21 Romagna F, Staniforth C-D (1989) The automated bone marrow micronucleus test. Mutat Res 213 91-104 Salamone M, Heddle J, Stuart E, Katz M (1980) Towards an improved micronucleus test. Mutat Res 74 347-356 Schmid W (1975) The micronucleus test. Mutat Res 31 9-15... 

Natarajan AT, Boei JJ (2004) Formation of chromosome aberrations insights from FISH. Mutation Res 544 299-304 OECD Guideline 475 (1997) Mammalian Bone Marrow Chromosome Aberration Test. Adopted July 21 Preston RJ, Dean BJ, Galloway S, Holden H, McFee AF, Shelby M (1987) Mammalian in vivo cytogenetic assays Analysis of chromosome aberrations in bone marrow cells. Mutation Res 189(2) 157-165... 

Tice RR, Hayashi M, MacGregor JT, Anderson D, Blakey DH, Holden HE, Kirsch-Volders M, Oleson JFB, Pacchierotti F, Preston RJ, Romagna F, Shimada H, Sutou S, Van-nier B (1994) Report from the Working Group on the in vivo mammalian bone marrow chromosome aberration test. Mutation Res 312 305-312... 

Based on evidence derived from a large array of assays such as bacterial reverse mutation test, mammalian bone marrow chromosome aberration test, dominant lethal assay, and UDS assay, atrazine was concluded to lack mutagenic potential. 

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