Chromosome aberrations, related

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). 

Results of methyl parathion assays involving effects on chromosomes have also been contradictory. For sister chromatid exchange, Waters et al. (1982) reported a positive response in Chinese hamster ovary cells only in the presence of metabolic activation system, while methyl parathion tested positive without a metabolic activation system in Chinese hamster V79 cells (Chen et al. 1981), cultured normal human lymphoid cells (Chen et al. 1981 Gomez-Arroyo et al. 1987 Sobti et al. 1982), and Burkitt s l5miphoma cells (Chen et al. 1981). Chen et al. (1981) found a significant dose-related increase in sister chromatid exchange in both hamster and human cultured cells, but dose-related cell cycle delays were less pronounced in human cell lines than in V79 cells. Negative results were obtained for chromosomal aberrations in human lymphocytes without a metabolic activation system (Kumar et al. 1993). 

The accident at the Chernobyl, Ukraine, nuclear reactor on April 26, 1986, contaminated much of the northern hemisphere, especially Europe, by releasing large amounts of radiocesium-137 and other radionuclides into the environment. In the immediate vicinity of Chernobyl at least 30 people died, more than 115,000 others were evacuated, and the consumption of locally produced milk and other foods was banned because of radiocontamination. The most sensitive local ecosystems were the soil fauna and pine forest communities. Elsewhere, fallout from Chernobyl measurably contaminated freshwater, marine, and terrestrial ecosystems, including flesh and milk of domestic livestock. Reindeer (Rangifer tarandus) calves in Norway showed an increasing frequency of chromosomal aberrations that seemed to correlate with cesium-137 tissue concentrations tissue concentrations, in turn, were related to cesium-137 in lichens, an efficient absorber of airborne particles containing radiocesium and the main food source of reindeer during winter. A pattern similar to that of reindeer was documented in moose (Alces) in Scandinavia. 

Connell, J.R. and Medcalf, A.S. (1982). The induction of SCE and chromosomal aberrations with relation to specific base methylation of DNA in Chinese hamster cells by N-methyl-n-nitrosourea and dimethyl sulphate. Carcinogenesis 3 385-390. 

There are several reports of noteworthy extrapulmonary effects in laboratory animals with concentrations of about 0.2 ppm. These include reduced voluntary activity, chromosomal aberrations in circulating lymphocytes of hamsters, increased neonatal mortality, and greater incidence of jaw abnormalities in offspring of ozone-exposed mice. The mechanisms of these reported effects and whether th are due to direct actions of absorbed ozone, some secondary reaction product, or secondary responses to the stress of local actions in the lung are largely unknown. However, reported analogous effects in humans exposed to ozone, such as changes in visual acuity and headache (possibly related to the reduced activity in... 

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). 

Mutagenesis Human peripheral blood lymphocytes were exposed to zalcitabine, and at 1.5 mcg/mL or more, dose-related increases in chromosomal aberrations were seen. Oral doses of zalcitabine at 2500 and 4500 mg/kg were clastogenic in the mouse micronucleus assay. 

Furthermore, each cell division round has the potential danger of rearrangement of chromosome sections during mitosis and thus chromosome aberrations. A thorough theoretical and experimental analysis of the dose-effect relation of various canceroge-nic substances has shown that an increased cell division activity is an important risk factor for the creation of tumors (Cohen and Ellwein, 1990). All processes that lead to an increase in the rate of cell division will increase the probability of tumor formation, according to these investigations. 

Bis(bromomethyl)propane-l,3-diol eaused a dose-related inerease in chromosomal aberrations in Chinese hamster ovary cells, but only at doses that eaused significant cytotoxicity a majority of the breaks were located in the heteroehromatie region of the long arm of ehromosome X, but the reasons for this are unclear. Induetion of sister chromatid exchanges in Chinese hamster ovary cells was judged to be equivoeal. 

Related Tests. Many cells exposed to test chemicals can be scored for chromosome aberrations by staining procedures followed by visual examination with the aid of the microscope. These include Chinese hamster ovary cells in culture treated in a protocol very similar to that used in the test for SCEs, bone marrow cells from animals treated in vivo, or lymphocytes from animals treated in vivo. The types of aberrations evaluated include chromatid gaps, breaks, and deletions chromosome gaps, breaks, and deletions chromosome fragments translocations and ploidy. 

R. Lindquist, S. Vitols, A. Ost, G. Gahrton and C. Peterson, Low-density lipoprotein receptor activity in human leukemic cells relation to chromosome aberrations, Acta Med. Scand. 217 (1985) 553-558. 

Vanadium compounds have an inhibitory effect against induced rat hepatocar-cinogenesis by limiting cell proliferation and chromosomal aberrations in the pre-neoplastic stages of the development of this cancer [169], These antineoplastic effects of vanadium could be related to the induction of apoptosis and selective DNA damage in tumor cells [170], Vanadate has also proven effective against induction of colon carcinomas [171]. A vanadium(III) cysteine compound has been shown to... 

Awa, A.A., S. Neriishi, T. Honda, M.C. Yoshida, T. Sofuni, and T. Matsui. Chromosome-aberration frequency in cultured blood-cells in relation to radiation... 

Adopting the ideas proposed by Wurgler and Kramers (1992) and Kurelec (1993), it is proposed that the setting of water or sediment PNEC values for genotoxins should be based on sublethal biological endpoints expressed as statistically robust ECx or NOEC values. In practice, this could include the in vivo measurement of reproduction, development, growth, or specific cytogenetic macrolesions (namely, micronuclei, aneuploidy, and chromosomal aberrations) since these are known to relate to adverse phenotypic outcomes (Brusick 1987 Jha 2004). 

Chromosomal aberrations include both numerical and structural aberrations. Numerical aberrations are changes in the number of chromosomes of the normal number characteristic of the animals utilized (aneugenicity). Structural aberrations are classified into two types, chromosome or chromatid aberrations (clastogenicity). 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. 

Tompa A, Major J, Jakab MG. 1994. Monitoring of benzene-exposed workers for genotoxic effects of benzene improved-working-condition-related decrease in the frequencies of chromosomal aberrations in peripheral blood lymphocytes. Mutat Res 304 (2) 159-165. 

Conner et al. (1987) did not observe any effect on sister chromatid exchange in bone marrow, alveolar macrophages, and lymphocytes of mice exposed to MIC however, cell cycling of lymphocytes and bone marrow cells from mice exposed to >15 ppm MIC was almost completely suppressed. On the other hand, MIC was found to be genotoxic in rats (Dutta et al, 1988) and caused dose-related increases in sister chromatid exchange as well as chromosomal aberrations in hamster ovary cells in addition to cell cycle delay in mice (Shelby et al, 1987). MIC has also been... 

Accelerated Mice (SAM) line being characterized by accelerated rate of accumulation of senescence features and essential (approximately two-fold) shortening of lifespan in relation to the animals of the control line [99]. SAM mice are characterized by multiple defects in the system of anti-oxidant defense and increased level of chromosomal aberrations in the stem cells [99,100]. Every day use of camosine by the animals of this line (100 mg/kg body weight) results in deceleration (or reversion) of senescence, increase in average lifespan (approximately by 20%) as well as favored the exterior of the animals [101-103]. 

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