Chromosome damage prediction

Langton K, Marchant CA. Improvements to the Derek for Windows prediction of chromosome damage. Toxicol Lett 2005 158(1 ) S36-S37. 

Even if the bone marrow is a well-perfused tissue, chemically unstable compounds and/or metabolites may not reach it in sufficient quantities to induce detectable effects (Brambilla and Martelli 2004 Morita et al. 1997). In a large collaborative study of I ARC carcinogens (groups 1, 2A, and 2B), the in vivo bone marrow micronucleus test easily detected compounds able to induce tumors in hematopoietic tissues and lung. In contrast, it predicted only 40% of liver carcinogens (Morita et al. 1997). To solve this issue, chromosome damage, especially micronuclei, can be measured in tissues other than bone marrow and peripheral blood erythrocytes (Hayashi et al. 2007). 

Describe the Ames test for mutagenicity. Does the Ames test predict carcinogenicity Chromosomal damage Explain. 

See Section 5.8.2 for a description of the Ames lest. Approximately 85% of carcinogenic chemicals are detected by the Ames test, i.e., the correlation between the Ames test for mutagenicity, on the one hand, and carcinogenicity tests in animals, on the other, is about 85%. The Ames test produces both false positives and false negatives. It is not able to predict chromosomal damage because it is performed in prokaryotes, which lack chromosomes. 

The contractile proteins of the spindle apparatus must draw apart the replicated chromosomes before the cell can divide. This process is prevented by the so-called spindle poisons (see also colchicine, p. 316) that arrest mitosis at metaphase by disrupting the assembly of microtubules into spindle threads. The vinca alkaloids, vincristine and vinblastine (from the periwinkle plant. Vinca rosea) exert such a cell-cycle-specific effect. Damage to the nervous system is a predicted adverse effect arising from injury to microtubule-operated axonal transport mechanisms. 

This usually means that the system should detect three major classes of mutation—genic, chromosomal, and genomic. Only with additional justification would other end points, such as chemical damage to DMA and mammalian cell transformation (neoplastic transformation), be recommended as part of a mutagenicity test battery. Such systems can be validated by demonstrating that they predict mutation. 

Prediction of carcinogenic potential of pesticides was taken a step further by Dr. S. Nesnow, who described EPA s "phased approach" for the application of short-term tests to these compounds. Phase 1 involved detection of point mutations, DNA damage and chromosomal effects in appropriate microorganisms. 

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