Chromosomal aberration study

No calculation of the RBE of the alpha rays at this very low dose range can be made, as no in vitro study was carried out with x- or gamma rays at such low dose levels. The lowest dose of x-rays with which a chromosome aberration study has been carried out was 4 mGy (Pohl-Riiling et al.t 1983) A very rough estimation of the RBE at doses between 2 and 4 mGy yield a value between 2 and 3 ... 

PNA was mutagenic in vitro in some bacterial strains and in chromosomal aberration studies. ... 

An advantage of this sort of test is that it is much easier and more rapid than dominant-lethal tests, chromosomal-aberration studies, and specific-locus mutation experiments. Because the test is done in vivo, activation of the test chemical is possible in the germ cells themselves or in other organs that might then release the active compound to the circulatory system and thereby cause an interaction with the germ cells. For most of the chemicals looked at, the measurement of DNA repair in mouse germ cells appears to be a considerably more sensitive biologic end point than measurement of dominant lethals or translocations. 

The chromosomal aberration study typically uses cells derived from Chinese hamster ovaries. These cells are encouraged to undergo mitosis, or cell division. They are then exposed to the test article and a chemical that stops the mitosis in metaphase stage. This is the stage in which all chromosomes are visible. At least 200 metaphase cells will be evaluated for visible damage to the chromosomes. 

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). 

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. 

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. 

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). 

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). 

Rasmussen K, Sabroe S, Wohlert M, et al. 1988. A genotoxic study of metal workers exposed to trichloroethylene Sperm parameters and chromosome aberrations in lymphocytes. Int Arch Occup Environ Health 60 419-423. 

No results indicating genotoxicity were observed in in vitro studies that examined six organophosphate ester hydraulic fluids for gene mutation, deoxyribonucleic acid (DNA) damage, or chromosomal aberrations in eukaryotes (see summarized data in Table 2-11). 

Monsanto. 1988a. In vitro chromosome aberration with Skydrol 500B-4 fire resistant hydraulic fluid study on butyldiphenylphosphate, dibutylphenylphosphate and tributylphosphate. 

Genotoxic Effects. Evaluation of the genotoxicity of lead in humans has focused on evaluations of lymphocytes from occupationally or environmentally exposed persons (Table 2-10) and in vitro studies of structural chromosomal aberrations and sister chromatid exchange in cultures of lymphocytes taken from healthy individuals (Table 2-11). Results of studies with human lymphocyte cultures exposed in vitro to lead acetate were nearly equally divided between positive (Beek and Obe 1974 Niebuhr and Wulf 1984) and negative (Beek and Obe 1975 Deknudt and Deminatti 1978 Gasiorek and Bauchinger 1981 Schmid etal. 1972). 

The main problems of the study of chromosome aberrations, caused by radon and daughters at their most frequently existing dose levels, i. e. boardering the natural burdens, ares (i) to get statistical significance at very low doses, and (ii) to study their induction by internal exposure to alpha emitters only. 

Kilibarda, M., B. Marcovic, and D. Panov, Studies of Chromosome Aberrations in Persons Chronically Exposed to Radiation (X, Ra 226, and Rn 222), Studies Biophysics 6 179-186 (1968). 

Factory workers exposed for an average of 15 years to acrylonitrile vapors showed no increase in chromosomal aberrations in the peripheral lymphocytes (Thiess and Fleig 1978). As in most human studies, the actual concentration of acrylonitrile to which these workers were exposed was not reported. Flowever, monitoring data indicated that the average exposure concentration for the workers was 5 ppm for the majority of the exposure period (approximately 10 years) at the time the study was conducted, acrylonitrile levels in the workplace had been reduced to 1.5 ppm. 

Grant WF (1994) The present status of higher plant bioassays for the detection of environmental mutagens. Mutat Res 310 175-185 Grant WF, Owens ET (2001) Chromosome aberrations in Pisum for the study of environmental mutagens. Mutat Res 488 93-118 Kalweit S, Utesch D, von der Hude W, Madle S (1999) Chemically induced micronucleus formation in V79 cells-comparison of three different test approaches. Mutat Res 439 183-190... 

An increased frequency of sister chromatid exchanges was obtained in vivo in bone-marrow cells of male Swiss mice at intraperitoneal doses of 210 and 420 mg/kg (Parodi et al. 1982, 1983) and in vitro Chinese hamster cells (Abe and Sasaki 1977), although in the latter study, no chromosomal aberrations were observed. 

Tributyltins and other organotins induce chromosomal aberrations in mammals, although this was not observed in tests with aquatic invertebrates (Dixon and Prosser 1986). Studies with isolated rat hepatoma cells, TBT, and PCB 126, show that TBT inhibits cytochrome P-4501A activity, and PCB 126 induces EROD activity. However, PCB-induced EROD activity was potentiated by coexposure to low noncytotoxic concentrations of TBT (Kannan et al. 1998b). Authors concluded that TBT does not interfere with Ah receptor binding and that potentiation of EROD activity and cytotoxicity as a result of coexposure to PCB 126 and TBT is significant because they coaccumulated in a variety of marine organisms. 

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