Chromosomes aberration

Tests for chromosome aberrations involve the estimation of effects on extended regions of whole chromosomes rather than on single or small numbers of genes. Primarily they concern chromosome breaks and the exchange of material between chromosomes. 

The test can also be carried out on cells treated in vivo, and analyses have been made of SCEs in lymphocytes from cancer patients treated with chemotherapeutic drugs, smokers, and workers exposed occupationally in several cases increased incidence of SCEs has been noted. This is a sensitive test for compounds that alkylate DNA, with few false positives. It may be useful for detecting promoters such as phorbol esters. 

Micronucleus Test The micronucleus test is an in vivo test usually carried out in mice. The animals are treated in vivo, and the erythrocyte stem cells from the bone marrow are stained and examined for micronuclei. Micronuclei represent chromosome fragments or chromosomes left behind at anaphase. It is basically a test for compounds that cause chromosome breaks (clastogenic agents) and compounds that interfere with normal mitotic cell division, including compounds that affect spindle fiber function. 

Male and female mice from an outbred strain are handled by the best animal husbandry techniques, as described for acute, subchronic, and chronic tests, and are treated either with the solvent, 0.5 LD50, or 0.1 LD50 of the test chemical. Animals are killed at several time intervals up to 2 days the bone marrow is extracted, placed on 

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. 

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A number of studies have shown that vitamins moderate the induction of chromosomal aberrations by radiation. Vitamins C and E given orally to mice either 2 h before, immediately after, or 2 h after 1 Gy (100 rad) of y-ray TBI significantly reduce the frequencies of micronuclei and chromosomal aberrations in BM cells. Vitamin E is the more effective (95). Administration of vitamins C and E within 5 min of irradiation is as effective as pretreatment. Protection by vitamin C has also been shown in humans. Whereas chronic treatment of rats using vitamin C (100 or 300 mg/(kg/d)) for six months prior to TBI protects against chromosomal aberrations, vitamin E is not radioprotective in this setting (96). 

Literature reports iadicate that sodium sorbate causes weak genotoxic effects such as chromosomal aberrations and mutations ia mammalian cells (172,173). This effect is thought to be caused by oxidative products of sodium sorbate ia stored solutions (173—175). The main oxidation product of sodium sorbate, 4,5-oxohexenoate, is mutagenic ia a Salmonella mammahan-microsome test (176). Sorbic acid and potassium sorbate were not genotoxic under the same test procedures (167,172,174—177). 

Ethylene oxide has been shown to produce mutagenic and cytogenic effects in a variety of test systems (226). An increased frequency of chromosomal aberrations in peripheral lymphocytes of monkey exposed to ethylene oxide for 104 weeks has been reported (240). In mice, it is an effective inducer of chromosome breaks leading to dominant-lethal mutations. In addition, ethylene oxide has been shown to induce heritable effects in the heritable translocation test conducted in mice exposed to ethylene oxide by inhalation (241,242). In this study, male mice were exposed to ethylene oxide ranging from 165 to 300 ppm for 6 h per day 5 or 7 days/week for 8.5 weeks. Ethylene oxide has also been shown to bind to proteins (243) as well as to DNA (244). Several studies on ethylene oxide-exposed workers have demonstrated an increased incidence of chromosomal aberrations and sister chromatid exchanges the relevance of such effects to human health evaluation is currendy uncertain. 

Assays for chromosome aberrations and micronuclei Assays for aneuploidy... 

Physiological effects of air pollution are deperrdent on dosage, the ability of the exposed organism to metabolize and excrete the pollution, and the type of pollutant. Many pollutants affect the futretiotring of the respiratory tract some change the structure and function of molecules others can enter the nucleus and turn getres otr or off atrd some cause chromosomal aberrations or mutations that result in cancer. 

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). 

In a case-control study of pesticide factory workers in Brazil exposed to methyl parathion and formulating solvents, the incidence of chromosomal aberrations in lymphocytes was investigated (De Cassia Stocco et al. 1982). Though dichlorodiphenyltrichloroethane (DDT) was coformulated with methyl parathion, blood DDT levels in the methyl parathion-examined workers and "nonexposed" workers were not significantly different. These workers were presumably exposed to methyl parathion via both inhalation and dermal routes however, a dose level was not reported. The exposed workers showed blood cholinesterase depressions between 50 and 75%. However, the baseline blood cholinesterase levels in nonexposed workers were not reported. No increases in the percentage of lymphocytes with chromosome breaks were found in 15 of these workers who were exposed to methyl parathion from 1 week to up to 7 years as compared with controls. The controls consisted of 13 men who had not been occupationally exposed to any chemical and were of comparable age and socioeconomic level. This study is limited because of concomitant exposure to formulating solvents, the recent history of exposure for the workers was not reported, the selection of the control group was not described adequately, and the sample size was limited. 

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. 

Mouse/oral exposure drinking water Chromosomal aberrations - Degraeve et al. 1985... 

Mouse/intraperitoneai administration Chromosomal aberrations - Huang 1973... 

Human lymphocytes/dermal and inhalation exposure Chromosomal aberrations - De Cassia Stocco et al. 1982... 

Human lymphocytes/oral exposure Chromosomal aberrations + Van Bao et al. 1974... 

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). 

Genotoxicity. No reliable data in humans exist to indicate whether methyl parathion may act by a genotoxic mechanism. One study reported a temporary but significant increase in chromatid breaks and stable chromosomal aberrations in two subjects after ingestion of methyl parathion (Van Bao et al. 1974), but another study reported no significant differences in five subjects after ingestion of methyl parathion when compared with 15 controls (Czeizel 1994). A study that involved combined inhalation and dermal exposure of workers to methyl parathion showed no increase in chromosomal aberrations in their... 

Since in vivo tests in exposed human populations would involve concomitant exposure to other toxicants, it would be difficult to assess the genotoxic potential of methyl parathion alone. Therefore, additional well-designed in vitro studies using human cell lines are needed to determine the effects of methyl parathion on various genotoxic parameters (e.g., sister chromatid exchange, chromosomal aberrations, unscheduled DNA synthesis). 

Das P, John G. 1999. Induction of sister chromatid exchanges and chromosome aberrations in vivo in Etroplus suratensis (Bloch) following exposure to organophosphorus pesticides. Toxicol Lett 104 111-116. 

De Ferrari M, Artuso M, Bonassi S, et al. 1991. Cytogenic biomonitoring of an Italian population exposed to pesticides Chromosome aberration and sister-chromatid exchange analysis in peripheral blood lymphocytes. Mutat Res 260 105-113. 

Dulout FN, Pastori MC, Olivero OA, et al. 1985. Sister-chromatid exchanges and chromosomal aberrations in a population exposed to pesticides. Mutat Res 143 237-244. 

Kumar KBS, Ankathil R, Devi KS. 1993. Chromosomal aberrations induced by methyl parathion in human peripheral lymphocytes of alcoholics and smokers. Hum Exp Toxicol 12 285-288. 

Malhi PK, Grover IS. 1987. Genotoxic effects of some organophosphoms pesticides 11. In vivo chromosomal aberration bioassay in bone marrow cells in rat. Mutat Res 188 45-51. 

Van Bao T, Szabo I, Ruzicska P, et al. 1974. Chromosome aberrations in patients suffering acute organic phosphate insecticide intoxication. Humangenetik 24 33-57. 

Oral administration of 11.6 mg/kg/day of endosulfan to rats for up to 30 days also failed to induce chromosomal damage in bone marrow and spermatogonial cell systems, but it is not known how soon after treatment the animals were killed. As shown in mouse studies (Usha Rani and Reddy 1986), a latency period of 60 days was required to see chromosomal aberrations in spermatogonia. However, relatively significant changes were observed for mitotic indices (Dikshith et al. 1978). 

In summary, endosulfan was not shown to be genotoxic following oral exposure of rats, but the data are inconclusive. It induces chromosomal aberrations and gene mutations in mice and Drosophila. Further... 

Mammalian cells Mouse spermatogonial cells Chromosomal aberrations + Usha Rani and Reddy 1986... 

Rat spermatogonial cells Chromosomal aberrations B Dikshith and Datta 1978 Dikshith et al. 1978... 

Hamster bone marrow Chromosomal aberrations + Dzwonkowska and Hubner 1986... 

Dzwonkowska A, Hubner H. 1986. Induction of chromosomal aberrations in the Syrian hamster by insecticides tested in vivo. Arch Toxicol 58 152-156. 

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