Sister-chromatid exchange increased frequency

In case of genotoxic carcinogens biomarkers include DNA-adducts, which are considered to be markers of exposure, and biomarkers of effects e.g. chromosomal aberrations, sister chromatid exchanges, increased frequency of micronuclei or mutations (Swenberg et al. 2008). Whereas biomarkers of exposure extrapolate down to zero, biomarkers of effect interpolate with the spontaneous or background number of mutations. Since exposure can be multiple and via different sources over a certain time several definitions are used ... 

In some studies the genetic effects on paint industry workers could not be detected when chromosomal aberrations and sister chromatid exchanges were studied. In other studies it was shown that the frequency of micronuclei and sister chromatid exchanges increased. 

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 an in vitro assay with cultured human fibroblasts, aniline produced only marginal increases in sister chromatid exchanges at the highest dose tested, 10 mM whereas two metabolites of aniline, 2-aminophenol and jV-phenylhydroxylamine, doubled the frequency of sister chromatid exchanges at the highest tested nontoxic concentration, 0.1 mM (Wilmer et al. 1981). 

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. 

Human cells exposed to various nickel compounds have an increased frequency of chromosomal aberrations, although sister chromatid exchange frequency is unaffected. Cells from nickel refinery workers exposed to nickel monosulfide (0.2 mg Ni/m3) or nickel subsulfide (0.5 mg Ni/m3) showed a significant increase in the incidence of chromosomal aberrations (Boysen et al. 1980 WHO 1991 USPHS 1993). No correlation was evident between nickel exposure level and the frequency of aberrations (USPHS 1993). 

Chinese hamster, Cricetus sp. ovary cells, single acute dose ranging between 0.005 and 0.06 Gy Increased frequency of sister chromatid exchange at 0.005 Gy increased numbers of chromosomal aberrations at >0.02 Gy no significant increase in cell death 10... 

Chlordecone (1.67-10.00 mg/L) increased the frequency of sister chromatid exchange in CHO cells but only in the absence of S9 activation and only in the presence of cell-cycle delay the results were confirmed in a repeat trial (Galloway et al. 1987). By contrast, chlordecone alcohol was negative for sister chromatid exchange induction both with and without S9 activation (Galloway et al. 1987). Subcytotoxic doses of mirex did not induce unscheduled DNA synthesis in primary hepatocytes recovered from rats, mice, or hamsters (Maslansky and Williams 1981 Williams 1980). Similar results were obtained by Probst et al. (1981) using primary rat hepatocytes exposed to 1,000 pmol/L mirex. Chlordecone was also uniformly negative in unscheduled DNA synthesis assays of primary rat hepatocytes (Probst et al. 1981 Williams 1980). 

Unscheduled DNA synthesis (UDS) in hepatocytes was not increased in rats exposed to chloroform at gavage doses 400 mg/kg in oil (Mirsalis et al. 1982). Exposure to 200 mg/kg/day chloroform in oil by gavage for 4 days increased sister chromatid exchange frequency in bone marrow cells of mice (Morimoto and Koizumi 1983). Other genotoxicity studies are discussed in Section 2.5. 

Cytogenetic evaluation of workers exposed to ammonia showed increased frequency of chromosome aberrations and sister chromatid exchanges. ... 

In genotoxic assays inorganic arsenicals are either inactive or weak mutagens but are able to produce chromosomal effects including aberrations and sister chromatid exchange in most test systems. Studies of exposed human have detected higher incidences of chromosomal aberrations in peripheral lymphocytes and increases in the frequency of micronuclei in the oral mucosa cells, urothelial cells, and peripheral blood lymphocytes. ... 

At concentrations of 10 and 100p,g/ml, calcium silicate significantly increased the frequencies of chromosomal aberrations and sister chromatid exchanges in peripheral human blood lymphocytes. ... 

Divinyl benzene was weakly genotoxic in vivo, inducing a dose-dependent increase in sister chromatid exchanges and an increase in the frequency of chromosome aberrations in male mice exposed at concentrations of up to 75 ppm for 3 days. ... 

Ethyl alcohol is not a bacterial or mammalian cell mutagen in vitro Increased frequencies of sister chromatid exchanges and aneuploidies have been observed in the peripheral lymphocytes of alcoholics." Although some degree of genotoxicity may result from excessive alcohol drinking, it is not considered relevant to occupational exposures. ... 

Most studies indicate that malathion is not genotoxic, although some tests indicate that it can produce chromosomal aberrations and sister chromatid exchanges in vitro There was no significant increase in mutation frequency or micronucleus formation in a cohort of California workers involved in application of malathion as ground treatment during the 1990s. ... 

Metabolism and genetic toxicity have been reported to differ with the isomer of nitro-toluene. p-Nitrotoluene was not mutagenic in bacterial assays, but it did increase sister chromatid exchange frequencies and chromosomal aberrations in vitro-, in vivo it did not increase the frequency of micronuclei in bone marrow of treated rodents. Similar findings were reported for the ortho isomer, except that it did not induce chromosomal aberrations in vitro. Only the ortho isomer induces DNA excision repair in the in vivo-in vitro hepatocyte unscheduled DNA synthesis assay. Furthermore, ort/jo-nitrotoluene binds to hepatic DNA to a much greater extent than meta- or para-nitrotoluene, and investigators suggest that it may act similarly to the rodent hepatocarcino-gen 2,6-dinitrotoluene. ... 

Occupational exposure of 20 workers to pentachlorophenol at concentrations that ranged from 1.2 to ISOpg /m for 3-34 years did not result in any increased incidence of sister chromatid exchanges or chromosomal aberrations. In another report, significant increases in the incidence of dicentric chromosomes and acentric fragments were detected in the peripheral lymphocytes of exposed workers the frequency of sister chromatid exchanges was not increased." ... 

In human lymphocyte culture assays rotenone did not increase the frequency of chromosomal aberrations or sister chromatid exchanges but did cause an increase in the frequency of binucleated micronuclei and a delay in cell cycle. ... 

Toxaphene has been found to be genotoxic in a number of assays. It was mutagenic in Sal-Ttimella typhimurium, and increased the frequency of sister chromatid exchanges in cell culture. In one study toxaphene-exposed individuals had a higher incidence of chromosomal aberrations in lymphocytes than controls. However, in vivo toxaphene did not bind to DNA or produce dominant lethal mutations. ... 

Triethanolamine was not genotoxic in a variety of assays." It was not mutagenic in Salmonella typhimurium and did not induce sister chromatid exchanges or chromosomal aberrations in vitro. In vivo there was no increase in the frequency of micronucleated erythrocytes in treated rodents. 

Vinyl chloride was genotoxic in a variety of in vitro assays. It is also reportedly mutagenic and clastogenic in humans. Increased frequencies of chromosomal aberrations, micronuclei, and sister chromatid exchanges have been found in the peripheral blood lymphocytes of workers exposed to high levels of vinyl chloride. ... 

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