Genotoxicity bone marrow chromosome aberration

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. 

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). 

In in vivo genotoxic assays o-dichloroben-zene induced micronuclei in the bone marrow of mice and was found to bind covalently to DNA, RNA, and proteins. Furthermore, a significant and persistent increase in chromosomal aberrations was observed in the peripheral blood of accidentally exposed workers. 

In genotoxic assays the cis isomer induced chromosomal aberrations in mouse bone marrow cells after intraperitoneal injections. Neither isomer was mutagenic in bacterial assays, nor did they produce chromosomal aberrations or sister chromatid exchanges in mammalian cells in vitroJ... 

Methyl methacrylate is not genotoxic in bacterial systems, but it has induced mutation and chromosomal aberrations in vitroP Increases in chromosomal aberrations in bone marrow cells of rats have been observed after in vivo inhalation exposure. ... 

In genotoxic assays, 2,6-xylidine induced sister chromatid exchanges and chromosomal aberrations in cultured mammalian cells but did not induce micronuclei in the bone marrow of mice treated in vivo conflicting results have been reported in the Salmonella typhimurium assay ... 

Oral in vivo animal studies provide convincing evidence that benzene is genotoxic. Tests on bone marrow cells, lymphocytes, and erythrocytes in mice gave positive results for chromosomal aberrations and micronuclei increases. Studies clearly demonstrate that, concerning micronuclei and chromosomal... 

In vivo and in vitro data from both humans and animals indicate that benzene and/or its metabolites are genotoxic. Chromosomal aberrations in peripheral lymphocytes and bone marrow cells are the predominant effects seen in humans (Ding et al. 1983 Fomi and Moreo 1967, 1969 Fomi et al. 1971a ... 

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... 

Genotoxic effects of trimethoprim on cultured human lymphocytes have been described (172). Chromosome studies performed in cultures of peripheral blood lymphocytes did not show significant differences before and after treatment. Cytogenetic studies on bone marrow cells from 12 patients with urinary tract infections treated with co-trimoxazole did not show structural chromosomal aberrations however, there was an increased number of micronuclei in these patients compared with controls (173). 

Ethene at atmospheric concentrations up to 20% was not mutagenic to one strain of Salmonella typhimur-ium with and without liver metabolic activation system (S9). In other strains of Salmonella in the presence and absence of S9, ethene was also negative. Ethene has shown no genotoxic activity in Escherichia coli. In nonbacterial tests, ethene did not induce chromosome aberrations in cultured Chinese hamster ovary cells exposed to 280.5 mgl in the presence and absence of S9, and did not induce micronuclei formation in bone marrow cells of rats or mice exposed up to 3000 ppm for 6 h day 5 days week for 4 weeks. 

In vivo studies (Table 2-4) have shown that NDMA methylates DNA, causes DNA fragmentation and induces DNA synthesis and repair in liver and other tissues of various species (e.g., rat, mouse, hamster, gerbil). NDMA induced chromosomal aberrations in hamster embryonic fibrolasts, sister chromatid exchanges in mouse bone marrow cells, and micronuclei in rat hepatocytes and rat and mouse bone marrow cells. The genotoxic effects indicated above occurred after inhalation, oral or intraperitoneal administration of NDMA. Sperm abnormalities were not seen in mice following intraperitoneal administration of NDMA. Sex linked recessive lethal mutations occurred in Drosophila melanoaaster. which indicates potential heritable mutagenicity of NDMA. 

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