Induction structural chromosome aberration

Kamiguchi Y., and K. Mikamo, Dose Response Relationship for Induction of Structural Chromosome Aberrations in Chinese Hamster Oocytes After X-Irradiation, Mutation Research 103 33-37 (1982). 

Positive results in the in vivo mammalian spermatogonial chromosome aberration test indicate that a substance induces structural chromosome aberrations in the germ cells of the species tested. This test measures chromosome events in spermatogonial germ cells and is, therefore, expected to be predictive of induction of inheritable mutations in germ cells. 

The induction of structural chromosome aberrations is classified in two types, chromosome or chromatid aberrations. The majority of induced aberrations are of the chromatid-type, but chromosome-type aberrations also occur. Chromosomal mutations and related events are the cause of many human genetic diseases and there is evidence that chromosomal mutations and related events are involved in cancer development. 

The oral administration of 500, 750, or 1,000 mg/kg/day unleaded gasoline (API PS-6) to groups of five male Sprague-Dawley rats for 5 consecutive days did not cause an increase in structural chromosome aberrations in bone marrow cells harvested 6 hours following the final treatment (Dooley et al. 1988). In general, animals orally exposed to gasoline did not exhibit unscheduled DNA synthesis (UDS) induction. The ability to induce UDS is a strong indication that a compound is... 

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). 

Conflicting results have been reported with respect to the induction of structural chromosome aberrations in peripheral blood lymphocytes from persons exposed to arsenic via drinking water (Ostrosky-Wegman et al. 1991, Dulout et al. 1996, Maki-Paakkanen etal. 1998). In industrial plants, all workers are generally exposed to a mixture of possible mutagens. Furthermore, the correlation between the frequency of aberrations and the level of arsenic was generally poor and the methodology sometimes questionable. It is, therefore, doubtful whether the anomalies observed were induced by arsenicals. 

Natarajan AT, Csukas, Degrassi F, Zeeland AA, Palitti F, Tanzarella C, Salvia R de, Fiore M (1982) Influence of inhibition of repair enzymes on the induction of chromosomal aberrations by physical and chemical agents. In Natarajan AT, Obe G, Altmann H (eds) DNA repair, chromosome alterations and chromatin structure. Prog Mutat Res 4 47-59... 

Induction of DNA single-strand breakage in rat liver after in-vivo exposure to N-nitrosodiethanolamine was demonstrated in three studies and dose-dependent effects were shown. In one of these studies, the DNA strand-breaking potential of 7V-nitroso-diethanolamine was found to be abolished by inhibition of sulfotransferase by 2,6-dichloro-4-nitrophenol. Unscheduled DNA synthesis was not detected in rats or mice in an in-vivo/in-vitro hepatocyte DNA repair assay after treatment with 7V-nitrosodi-ethanolamine. A single study in mice exposed in vivo to 7V-nitrosodiethanolamine did not find any significant induction of structural or numerical chromosomal aberrations or micronuclei in bone-marrow cells. 

Mutagenicity M-CASE Model A2E Structural alerts for DNA reactivity M-CASE Model A62 Induction of micronuclei TOPKAT Salmonella (Ames) mutagenicity M-CASE Model A2H Salmonella (Ames) mutagenicity M-CASE Model A61 Chromosomal aberrations M-CASE Model A2F Mutations in mouse lymphoma... 

Micronucleus assay 3D human reconstructed skin models Micronuclei induction Structural and numerical chromosome aberrations Genotoxicity hazard identification... 

Doxorubicin is an antineoplastic/anthracycline antibiotic. It binds DNA and inhibits nucleic acid synthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclear chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, and induction of mutagenesis and chromosomal aberrations. It is indicated in treatment of ovarian cancer in patients whose disease has progressed or recurred after platinum-based chemotherapy and in treatment of AIDS-related Kaposi s sarcoma in patients whose disease has progressed on prior combination chemotherapy or who are intolerant to such therapy. 

Ballarini F, Ottolenghi A. Models of chromosome aberration induction an example based on radiation track structure. Cytogenet Genome Res 2004 104(l-4) l49-56. 

Rosenkranz HS, Ennever FK, Dimayuga M, et al. 1990. Significant differences in the structural basis of the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells. Environ Mol Mutagen 16(3) 149-177. 

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