Chromosome aberration assays

Kanaya N, Gill BS, Grover IS, Murin A, Osiecka R, Sandhu SS, Andersson HC (1994) Vicia faba chromosomal aberration assay. Mutat Res 310 231-247 Matsuda H, Ose Y, Nagase H, Sato T, Kito H, Sumida K (1991) Mutagenicity of the components of ozonated humic substance. Sci Total Environ 103 129-140... 

No information on genotoxicity in humans was located. In vitro, chromosome aberration assays were negative with human lymphocytes at vapor concentrations of 1.25% to 35% v/v incubation times ranged from 3 to 24 h (Millischer et al. 1995). 

Chromosomal Physical damage to chromosomes (large ordered Chromosomal aberration assay assesses the potential for... 

Scott, D., Danford, N., Dean, B., Kirkland, D. and Richardson, C. (1983). In vitro chromosome aberration assays. In UKEMS Subcommittee on Guidelines for Mutagenicity Testing, Report Part I, Basic Test Battery (Dean, B.J., Ed.). UKEMS, Swansea, U.K., pp. 63-86. 

Mutagenesis A clastogenic effect was produced in an in vitro chromosomal aberration assay in Chinese hamster ovary cells. 

A positive result from a chromosome aberration assay (MNT, cytogenetic analysis or small colonies in MLA) suggests a second in vivo assay for clastogenesis or aneugenesis. Centromere staining of mitotic cells allows the distinction of aneugens and clastogens. 

Chloro-ort/20-toluidine gave variable results in the majority of bacterial tests for mutagenicity. While most of the mammalian tests were positive, chromosomal aberration assays gave conflicting results. These data overall indicate that 4-chloro-ort/2o-toluidine causes DNA damage in mammalian cells. 

Several bacterial and mammalian short-term tests for genetic toxicity as well as their biochemical and genetic rationale are described in Chapter 21 on toxicity testing. They include the salmonella assay, the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase assay, the mouse lymphoma assay, the mammalian transformation assay, sister chromatid exchange, and the chromosome aberration assay. 

In general, genotoxicity standard assays (e.g., bacterial reverse mutation assay [Ames test], in vitro chromosomal aberration assay, mouse lymphoma gene mutation assay, and rodent micronucleus assay) may not be suitable assays because the test cells do not contain the appropriate receptors to transport the product (i.e.,not a relevant species) or because the biopharmaceutical... 

Twenty-seven out of 44 FDA-approved biopharmaceuticals have been tested in a battery of genotoxicity assays. Eighty-five different assays performed yielded negative results. The most commonly performed assays were the Ames test, the chromosomal aberration assay in human lymphocytes, the mouse lymphoma gene mutation assay, and the mammalian in vivo erythrocyte micronucleus test. Examples of the range of biopharmaceutical products tested include, domase alfa (deoxyribonuclease I-DNAse), trastuzumab (mAb to human epidermal growth factor receptor 2), alteplase (tissue plasminogen activator), infliximab (mAb to the human tumor necrosis factor a). 

No rodent bioassay Not genotoxic (Ames or in vitro chromosomal aberrations assay (V79))... 

Not clastogenic (in vitro chromosomal aberration assay and in vivo mouse MN)... 

Prenatal and postnatal development none Genetic toxicology0 Ames test, human lymphocyte chromosomal aberration assay, CHO/HGPRT gene mutation assay, mouse micronucleus assay Carcinogenicity none... 

Developmental cynomolgus monkeys Prenatal and postnatal development cynomolgus monkeys Genetic toxicology Ames test, chromosome aberration assay in human peripheral lymphocytes, in vivo mouse micronucleus Carcinogenicity none... 

Fertility and early embryonic development rats Developmental rats, rabbits Prenatal and postnatal development rats Genetic toxicology Ames test, in vitro mammalian chromosome aberration assay, in vivo cytogenetic test, FIGPRT test with V79 cells... 

For a discussion of the result of the chromosome aberration assay the following parameters need to be considered a) comparison of the data from the treatment group versus concurrent negative control data and historical control data b) statistical analysis of the experimental data using trend analysis or pair-wise comparison (treatment group versus control). It is also recommended to check the variance between the animals and gender. However, for the final assess-... 

MILLER B, POTTER-LOCKER E, SEELBACH A, STOPPER H, UTESCH D and MADLE S (1998) Evaluation of the in vitro micronucleus test as an alternative to the in vitro chromosomal aberration assay position of the GUM Working Group on the in vitro micronucleus test. Gesellschaft fur Umwelt-Mutations-Forschung, Mutat Res. 410, 81-116. 

The potential for interaction with genetic material (and therefore risk of carcinogenicity) can be investigated using bacterial and mammalian gene mutation assays and chromosomal aberration assays. The parent CDs do not exhibit mutagenic behavior in any of these assays, and there have been no reports of tumors in oral feeding studies or in the parenteral administration of any of the parent CDs. 

Ethyl acetate induced aneuploidy in Sac-charomyces cerevisiae. It yielded positive results in an in vitro sister chromatid exchange assay in Chinese hamster ovary cells. In vitro chromosomal aberration assays were positive in Chinese hamster fibroblast cells and negative in Chinese hamster ovary cells. (An in vivo bone marrow micronucleus study in Chinese hamsters yielded negative results by both intraperitoneal and oral administrations.)... 

In in vitro (bacterial reverse mutation, CHO/ HGPRT forward mutation, and rat lymphocyte chromosomal aberration assays) and in vivo (mouse bone marrow micronucleus assay) tests, fexofenadine hydrochloride revealed no evidence of mutagenicity. 

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