Animals, chromosome aberration

The d(minanUlethal test consists of the administration of chemicals into the male animal, subsequent mating with an untreated female, and dissection and examination of the pregnant animal. Chromosome aberrations or dominant-lethal mutations cause the death of the embryos. This method has been used most successfully with mice, and is not too expensive to conduct. 

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). 

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). 

Investigations with Animals. A further support of the hypothesis described above can be found in investigations carried out with animals Leonard et al. (1979) found in an area with high natural radioactivity in France a small but significant increase of chromosome aberrations in the lymphocytes of rabbits. The rabbits were kept in a hut for 12 months, and received up to 0.7 Gy/year from gamma rays together with more than 6 Gy alpha doses from radon and daugthers. Further experiments with rabbits at radon exposure under controlled conditions have shown that the chromosome... 

Nitro PAHs have been shown to exhibit a large variety of biological activities. Included in these are the induction of mutations in bacterial (Table I) and eukaryotic cells (9,17,54-57), the neoplastic transformation of cultured mammalian cells (58-59), and the induction of DNA strand breaks (60), DNA repair (61-62), sister chromatid exchanges (63-64), and chromosomal aberrations (65-66). Nitro PAHs have also been demonstrated to bind cellular DNA in bacteria (67-73) and mammalian cells (74-77), to inhibit preferentially the growth of repair-deficient bacteria (78), to have recombinogenic activity in yeast (66,79-80) and to induce tumors in experimental animals (Table II). 

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. No studies were located regarding the genotoxicity of 1,2-diphenylhydrazine in humans by any route of exposure. A limited number of assays have been conducted using bacteria, mammalian cell and whole animal systems. As indicated in Table 2-2, 1,2-diphenylhydrazine was mutagenic in Salmonella typhimurium, out not in Escherichia coli, and produced chromosome aberrations and sister chromatid exchanges in Chinese hamster cells. An exogenous metabolic activation system was necessary for expression of the aforementioned effects. In in vivo studies... 

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). 

Chlorate is mutagenic in Salmonella and induces chromosome aberrations and micronuclei in mammalian cells [78]. It has also been shown to induce thyroid tumors in laboratory animals [79]. The U.S. LFA has placed chlorate on the current CCL-3 [54], as well as its Umegulated Contaminant Monitoring Rule-3 (UCMR-3) [80] to collect further national data, and is currently considering it for regulation. 

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. 

Positive results in the mammalian in vivo bone marrow chromosome aberration test indicate that a substance induces stmctural chromosome aberrations in the bone marrow of the species tested. An increase in polyploidy (a multiple of the haploid chromosome number (n) other than the diploid number, i.e., 3n, 4n and so on) may indicate that a substance has the potential to induce numerical aberrations (change in the number of chromosomes from the normal number characteristic of the animals utilized). 

Chrysene was mutagenic to Salmonella typhimurium in the presence of an exogenous metabolic system. It induced sister chromatid exchanges in one mouse study and chromosomal aberrations in one hamster study. Chrysene is metabolically activated to a 1,2-diol-3,4-epoxide that is mutagenic and carcinogenic in experimental animals and forms covalent adducts with DNA. ... 

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. 

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