Detecting Chromosome Aberrations

High doses of LSD may cause chromosome damage in experimental animals (Dishotsky et al. 1971). Chromosomal aberrations in humans have been related to drug abuse in general. Pharmacologically pure LSD, however, has not been demonstrated to cause a detectable increase in chromosome damage (Li and Lin 1998). 

Chromosome aberrations were detected in lymphocytes of individuals acutely intoxicated by methyl parathion by the inhalation route (Van Bao et al. 1974). Blood samples were taken 3-6 days after exposure and again at 30 and 380 days. A temporary but significant (p<0.05) increase was noted in the frequency of stable chromosomal aberrations in the exposed individuals. The study limitations include small sample size, absence of a control group, lack of quantification of exposure levels, and a possible concomitant exposure to other substances via the dermal route. 

Grant WF (1994) The present status of higher plant bioassays for the detection of environmental mutagens. Mutat Res 310 175-185 Grant WF, Owens ET (2001) Chromosome aberrations in Pisum for the study of environmental mutagens. Mutat Res 488 93-118 Kalweit S, Utesch D, von der Hude W, Madle S (1999) Chemically induced micronucleus formation in V79 cells-comparison of three different test approaches. Mutat Res 439 183-190... 

Chromosomal abnormalities and sister chromatid exchanges have been observed in mice following intraperitoneal administration of 1,2-dibromoethane (Krishna et al. 1985). Such chromosomal aberrations were also detected in vitro using human lymphocytes (Tucker et al. 1984) however, in... 

Gray, J. W., Kuo, W. L., and Pinkel, D. (1991) Molecular cytometry applied to detection and characterization of disease-linked chromosome aberrations. Baillieres Clin. Haematol. 4, 683-693. 

Gene mapping detection of heteromorphisms and determination of parental origin of heteromorphisms Detection of gene mutations Characterization of structural aberrations Identification of marker chromosomes Characterization of tumor cells Chromosome and karyotype evolution Spatial topography of chromosomes... 

Cremer, T., Lichter. P., Borden, J., Ward, D. C., and Manuelidis, L. (1988) Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome specific library probes. Hum. Genet. 80, 235-246. 

Genotoxic effects have been reported in animals treated with 3,3 -dichlorobenzidine. A single dose of 3,3 -dichlorobenzidine (1,000 mg/kg) administered to male and pregnant female mice induced micronuclei in polychromatic erythrocytes in the bone marrow of the males and in the liver of the fetuses, but not in bone marrow of the dams (Cihak and Vontorkova 1987). A micronucleus test is performed to detect a chemical s ability to induce chromosomal aberrations. However, the relevance of micronuclei formation to human health is not known. The reason for the lack of effect of 3,3 -dichlorobenzidine on bone marrow micronuclei formation in the mothers is unclear, but it may be related to deficiencies in the metabolic activation of 3,3 -dichlorobenzidine in female mice. The relative importance of pregnancy is unknown since the study did not evaluate nonpregnant females. In another study, an increase in unscheduled deoxyribonucleic acid synthesis (UDS) was observed in cultured liver cells from male mice previously pretreated orally with single doses of 500 mg/kg 3,3 -dichlorobenzidine no response was observed at a dose of 200 mg/kg (Ashby and Mohammed 1988). 

The bone marrow test is used for the detection of structural chromosome aberrations induced by a test substance in bone marrow cells of animals. A structural chromosome aberration is a change in chromosome structure detectable by microscopic examination of the metaphase stage of cell division, observed as deletions and fragments, intrachanges or interchanges. 

Chromosomal mutations are recognised as morphological alterations in the gross structure of chromosomes, that is, they are structural aberrations which can be detected microscopically. Compounds which cause chromosome damage are called clastogens. 

In genotoxic assays inorganic arsenicals are either inactive or weak mutagens but are able to produce chromosomal effects including aberrations and sister chromatid exchange in most test systems. Studies of exposed human have detected higher incidences of chromosomal aberrations in peripheral lymphocytes and increases in the frequency of micronuclei in the oral mucosa cells, urothelial cells, and peripheral blood lymphocytes. ... 

Occupational exposure of 20 workers to pentachlorophenol at concentrations that ranged from 1.2 to ISOpg /m for 3-34 years did not result in any increased incidence of sister chromatid exchanges or chromosomal aberrations. In another report, significant increases in the incidence of dicentric chromosomes and acentric fragments were detected in the peripheral lymphocytes of exposed workers the frequency of sister chromatid exchanges was not increased." ... 

In one animal study, a significant increase in lung tumors was observed in female mice exposed by inhalation. Available data indicate a genotoxic potential for sulfur dioxide. Increases in chromosome aberrations and sister chromatid exchanges have been detected in occupationally exposed workers. The lARC has determined that there is limited evidence for the carcinogenicity of sulfur dioxide in experimental animals and inadequate evidence in humans. 

Microbes and metazoans are exposed to a variety of toxic stresses and have evolved appropriate defenses and repair mechanisms. Some of these systems are regulated at the protein level, but others are regulated at the transcriptional level, allowing the development of reporter assays. These transcriptional responses can be used to provide an earlier marker for genotoxin exposure in a whole population of cells, rather than the detection of the endpoints discussed above, in which genotoxic stress leads to fixation of mutations or chromosomal aberrations/damage in a small subpopulation. 

Chromosomal aberrations were not induced by di(2-ethylhexyl) phthalate in any of eight studies in various types of cultured cells in the absence of metabolic activation. Only three of these studies for chromosomal aberrations included an exogenous metabolic activation system. Of these, one, using Syrian hamster embryo cells, found an increase in aberration frequency. Weak effects were detected for the induction of aneuploidy and mitotic division aberrations in Chinese hamster lung cells. 

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. 

In mammalian assays, glycidol has been tested in human lymphocytes and Chinese hamster cells in vitro for induction of chromosomal aberrations and sister chromatid exchanges. It was also tested in vivo in the mouse micronucleus assay. All test results were positive, as were those of gene mutation assays using Chinese hamster V79 cells and mouse lymphoma L5178Y cells. An in-vivo assay to detect chromosomal aberrations in mouse bone-marrow cells gave negative results. 

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