Chromosome change

Aplastic anemia and leukemia are not the only health effects ascribed to benzene exposure. A number of recent studies have associated benzene exposure with chromosomal changes (aberrations) (118). Other studies have shown abnormalities in porphyrin metabolism and decrease in leucocyte alkaline phosphatase activity in apparendy healthy workers exposed to 10—20 ppm benzene (119,120). Increases in leukoagglutinins, as well as increases in blood fibrinolytic activity, have also been reported and are believed to be responsible for the persistent hemorrhages in chronic benzene poisoning (121,122). 

Gasiorek K, Bauchinger M. 1981. Chromosome changes in human lymphocytes after separate and combined treatment with divalent salts of lead, cadmium, and zinc. Environ Mut 3 513-518. 

Sugimura H. Detection of chromosome changes in pathology archives an application of microwave-assisted fluorescence in situ hybridization to human carcinogenesis studies. Carcinogenesis 2008 29 681-687. 

In rats, nickel carbonyl is reported to cause dominant lethal mutations (WHO 1991), but this needs verification. Nickel sulfate, when given subcutaneously at 2.4 mg Ni/kg B W daily for 120 days causes infertility testicular tissues are adversely affected after the first injection (USEPA 1980). Nickel salts given intraperitoneally to rats at 6 mg Ni/kg BW daily for 14 days did not produce significant chromosomal changes in bone marrow or spermatogonial cells (Mathur et al. 1978). 

Howard, W., B. Leonard, W. Moody, and T.S. Kochhar. 1991. Induction of chromosome changes by metal compounds in cultured CHO cells. Toxicol. Lett. 56 179-186. 

This section presents basic information about gene mutations, chromosomal changes, and conditions that run in families.7... 

Sincock, H., and M. Seabright (1975). Induction of chromosome changes in Chinese hamster lungs by exposure to asbestos fibers. Nature 257 556—558. 

Mateuca, R., Lombaert, N., Aka, P.V., Decordier, 1. and Kirsch-Volders, M. (2006) Chromosomal changes induction, detection methods and applicability in human biomonitoring. Biochimie, 88, 1515-1531. 

If a mutation or major chromosomal change occurs and is not repaired, it may not be compatible with the continued existence of the cell and as already discussed above, cell death may occur by apoptosis. However, if the mutation is not lethal and not repaired, when the cell divides and the DNA replicates, the mutation will be passed on to the daughter cells and "fixed" in the genome. If the mutation is simply an altered base, at replication it will be corrected in one half of the molecule but compounded in the other. 

Bauchinger, M., Dresp, J., Schmid, E. Haug, R. (1982) Chromosome changes in lymphocytes after occupational exposure to pentachlorophenol (PCP). Mutat. Res., 102, 83-88... 

TCDD receptor) following a single intraperitoneal injection of 2,3,7,8-TCDD at doses of 50, 100, or 150 g/kg (Meyne et al. 1985). The samples were examined within 8-48 hours. The negative results may, however, have been due to the time-dependent detectability of chromosomal changes after CDD exposure reported earlier (Loprieno et al. 1982). 

In addition to studies dealing with structural chromosomal changes, effects on DNA were also investigated. Oral exposure to 1 g/kg/week of 2,3,7,8-TCDD or 1,2,3,7,8-PCDD for up to 6 months did not increase the formation of DNA adducts in Sprague-Dawley rats (Randerath et al. 1989). A single oral dose of 2,3,7,8-TCDD (25-100 g/kg) caused time-dependent increases in the induction of DNA single-strand breaks (and lipid peroxidation) in hepatic cells of Sprague-Dawley rats terminated within 3-14 days after the treatment (Wahba et al. 1989). 

Rowley JD, Golomb HM, Dougherty C. 15/17 Translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet 1977 1(8010) 549-550. 

Mammalian cells in culture permit several end points to be measured simultaneously in the same cell system. These include malignant transformations, chromosomal changes, and DNA damage and repair, as well as specific-locus mutation.26... 

Figure 2-7. Chromosomal changes caused by toxic chemicals on the mammalian cell system in in vitro.

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