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OECD 475: Bone marrow chromosomal aberration test (mammalian)

Chromosome mutations are the cause of many genetic diseases in humans. Cancer is associated with alterations in oncogenes and tumor suppressor genes. The mammalian in vivo chromosome aberration test is used for the detection of structural chromosome aberrations induced by test compounds in bone marrow cells of animals. Rats, mice and Chinese hamsters are commonly used.

The two types of structural chromosome aberrations are chromosome or chromatid. There are several criteria for determining a positive result, such as a dose-related increase in the relative number of cells with chromosome aberrations. Animals are exposed to the test compound and are treated with a metaphase-arresting agent (e.g., colchicine or Colcemid®) prior to euthanasia at appropriate times after treatment.

Bone marrow cells are harvested and stained, and metaphase cells are analyzed for chromosome aberrations. Each treated and control group must include at least 5 analyzable animals per sex. The limit dose for treatment up to 14 days is 2000 mg/kg/body weight/day, and for treatment longer than 14 days is 1000 mg/kg/body weight/day.

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