Chromosomal alterations

For patients with myelodysplastic syndrome or AML as a secondary neoplasm, there are a number of key features characteristic of the leukemia. Alkylator-related secondary leukemias after Hodgkin s disease usually have a myelodysplastic prodrome and a monosomy 5 or monosomy 7. Secondary ANLL with the use of epipodophyllotoxin (etoposide) demonstrates mainly M4 or M5 morphology and exhibits translocations within the MLL gene with 1 lq23 chromosomal alterations.8... 

The capacity of some agent or chemical substance to induce genetic changes resulting from chromosomal alterations, which changes may be transmitted from parent to offspring. 

Conway K, Costa M. 1989. Nonrandom chromosomal alterations in nickel-transformed Chinese hamster embryo cells. Cancer Res 49 6032-6038. 

F4. Falini, B., and Mason, D. Y., Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia Clinical value of their detection by immunocytochemistry. Blood 99, 409-426 (2002). 

Many chromosomal alterations can be detected in plants,149 and, in addition to studies of mitotic cells, methods using microsporocytes (i.e., pollen mother cells) have permitted the study of meiotic cells.263 Although basic research in plant cytogenetics continues, cytogenetic tests in plants have been replaced to some extent in genetic toxicology by mammalian cell-culture tests and tests in whole mammals. 

Resistance develops due to the ability of DNA to 1) undergo spontaneous mutation, or 2) move from one organism to another. In the first instance, chromosomal alteration may occur by insertion, deletion or substitution of one or more nucleotides within the genome1. 

Genetic toxicology studies These studies designed to identify potential point mutations, and/or clastogenic damage/chromosomal alterations are required for pharmaceuticals but generally not required for biopharmaceuticals, since they are not applicable for proteins. 

Purpose What is the potential of a test article with and without metabolic activation to induce structural chromosome alterations in Chinese hamster ovary (CHO) cells ... 

Structural and Numerical Alterations. The basic principles underlying in vivo cytogenetic assays are the same as those for in vitro assays, discussed above (Section 25.3.4b). The cell types that are available for the analysis of chromosome alterations are those that are cycling cell populations, such as bone marrow and spermatogonial cells. For acute exposures, analysis of metaphase cells at their first metaphase after S-phase treatment and analysis of all aberration types is appropriate for hazard evaluation. For chronic exposures, it is inappropriate to analyze unstable aberration types the informative approach is to analyze stable types (e.g., reciprocal translocations and inversions) using FISFI. 

For numerical chromosomal alterations, it is possible to analyze interphase cells using FISH with whole chromosome paints, or chromosomal specific probes. Thus, it is feasible to assess nondisjunctional events in any cell type, including target cells for tumorigenesis. Other fluorescence-based methods described in the section on in vitro methods (Section 25.3.4b) can be used in vivo, but they are of rather limited value for basic mutagenicity assays. 

Eastmond, D.A. University of California Riverside, CA Chromosomal alterations induced in mice and humans Health Effects Institute... 

Biesele, J., Philips, F., Thiersch, J., Burchenal, J., Buckley, S., Stock, C., Loveless, A., Ross, W. (1950). Chromosome alteration and tumour inhibition by nitrogen mustards the hypothesis of crosslinking alkylation. Nature 166 1112-14. 

Dopp E, Schiffinann D. 1998. Analysis of chromosomal alteration induced by asbestos and ceramic fibers. Toxicol Lett 96 155-162. 

Chromosomal alterations and oncogene/suppressor gene involvement... 

Such specific identification of aberrations has made it possible, in some cases, to determine which environmental insult is responsible for the chromosome alterations. The chromosome aberrations thus become biomarkers of exposure. 

Moore LE, Smith AH, Emg C, et al. Arsenic-related chromosomal alterations in bladder cancer. J Natl Cancer Inst 2002 94(22) 1688-96. 

In silico approaches to prediction of aqueous and DMSO solubility of drug-like compounds trends, problems and solutions. Current Medicinal Chemistry, 13 (2), 223-241 Meltzer, P.S., Kallioniemi, A. and Trent, J.M. (2002) Chromosome alterations in human solid tumors, in The Genetic Basis of Human Cancer (eds B. Vogelstein and K.W. Kinzler), McGraw-Hill, New York, pp. 93-113. 

---