Validation of a flow cytometric in vitro DNA repair (UDS) assay in rat hepatocytes

Selden, Jules R.; Dolbeare, Frank; Clair, James St.; Miller, Judith E.; McGettigan, Katherine; DiJohn, John A.; Dysart, Gary; DeLuca, John G.

doi:10.1016/0921-8777(94)90015-9

Cited by 29 publications

(11 citation statements)

References 23 publications

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“…CT was also reported to impede chromosome segregation and result in aneuploidy [Coutino, 1979;Onfelt, 1987]. CT exhibited negative or equivocal results in studies of unscheduled DNA synthesis (UDS) in primary rat and human hepatocytes [Butterworth et al, 1989;Selden et al, 1994]. It did not induce mutations at the tk locus when tested in mouse lymphoma L5178Y cells [Wangenheim and Bolcsfoldi, 1988] and yielded equivocal results when assayed for its ability to induce morphological transformation in early studies using Syrian hamster embryo cells [Amacher and Zelljadt, 1983].…”

Section: Overview Of the Genotoxicity And Mutagenicity Studies On Ctmentioning

confidence: 98%

Evaluating genotoxicity data to identify a mode of action and its application in estimating cancer risk at low doses: A case study involving carbon tetrachloride

Eastmond

2008

Environ and Mol Mutagen

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In the new USEPA cancer risk assessment guidelines, mode of action (MoA) information, combined with a determination of whether or not a chemical is mutagenic, plays an important role in determining whether a linear or nonlinear approach should be used to estimate cancer risks at low doses. In this article, carbon tetrachloride (CT) is used as an example to illustrate how mixed genotoxicity data can be evaluated and used to identify a likely MoA. CT is essentially negative in inducing gene mutations in Salmonella, but is consistently positive in inducing recombination and aneuploidy in fungi. Negative or equivocal results were seen in most in vitro and in vivo studies in mammals, including mutation studies in transgenic mice. However, DNA adducts, primarily those derived from oxidation- and lipid-peroxidation-derived products as well as DNA double-strand breaks and micronucleated cells, have been seen repeatedly in the liver of CT-treated animals. On the basis of the weight of evidence, CT should not be considered a directly mutagenic agent. Mutagenic as well as other genotoxic effects, as they occur, will most likely be generated through indirect mechanisms resulting from oxidative and lipid peroxidative damage and/or damage occurring during necrosis or apoptosis. As key events in this process are expected to occur in a nonlinear fashion, the expected relationship between CT dose and carcinogenic response in the liver is likely to be nonlinear with a steep dose response. This conclusion is consistent with rodent cancer bioassay results in which steep nonlinear dose responses have been seen.

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Section: Overview Of the Genotoxicity And Mutagenicity Studies On Ctmentioning

confidence: 98%

Evaluating genotoxicity data to identify a mode of action and its application in estimating cancer risk at low doses: A case study involving carbon tetrachloride

Eastmond

2008

Environ and Mol Mutagen

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“…There have been some suggestions that BrdU labels cells undergoing DNA repair, in addition to those in mitosis (Rakic, 2002a,b). This seems unlikely however, because DNA repair usually involves the synthesis of only 3-100 nucleotides per lesion (Selden et al, 1994), while the entire genome (2.5 billion nucleotides) is synthesized during the S-phase of mitosis. This huge (nearly a billion-fold) difference is so large that the two processes should always be easy to discriminate.…”

Section: Bromodeoxyuridinementioning

confidence: 98%

Neurogenesis in the adult hippocampus

2006

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The dentate gyrus (DG) contains one of the few neuronal populations in the mammalian brain that are generated throughout life. Research into the regulation and function of adult neurogenesis continues its rapid growth in popularity. With the researcher new to the field in mind, we review the processes that together constitute adult neurogenesis and some of the methods most commonly used for studying these processes. (c) 2006 Wiley-Liss, Inc.

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“…Figure 5 shows flow cytometric analysis of the increased incorporation of BrdUrd into the G0/G1 region of the BrdUrd/DNA bivariate distribution after human diploid fibroblasts (IMR-90) were exposed to 4-nitroquinoline oxide, ICR-170 (acridine orange), ethyl methane sulphonate, or methyl methane sulphonate. In an additional study, Selden et al (1994) developed an in vitro rat hepatocyte assay for evaluating DNA repair following the application of a number of chemical mutagens and carcinogens. Srivastava et aI.…”

Section: Dna Repairmentioning

confidence: 99%

Bromodeoxyuridine: a diagnostic tool in biology and medicine, Part III. Proliferation in normal, injured and diseased tissue, growth factors, differentiation, DNA replication sites andin situ hybridization

Dolbeare

1996

Histochem J

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This paper is a continuation of parts I (history, methods and cell kinetics) and II (clinical applications and carcinogenesis) published previously (Dolbeare, 1995 Histochem. J. 27, 339, 923). Incorporation of bromodeoxyuridine (BrdUrd) into DNA is used to measure proliferation in normal, diseased and injured tissue and to follow the effect of growth factors. Immunochemical detection of BrdUrd can be used to determine proliferative characteristics of differentiating tissues and to obtain birth dates for actual differentiation events. Studies are also described in which BrdUrd is used to follow the order of DNA replication in specific chromosomes, DNA replication sites in the nucleus and to monitor DNA repair. BrdUrd incorporation has been used as a tool for in situ hybridization experiments.

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Validation of a flow cytometric in vitro DNA repair (UDS) assay in rat hepatocytes

Cited by 29 publications

References 23 publications

Evaluating genotoxicity data to identify a mode of action and its application in estimating cancer risk at low doses: A case study involving carbon tetrachloride

Evaluating genotoxicity data to identify a mode of action and its application in estimating cancer risk at low doses: A case study involving carbon tetrachloride

Neurogenesis in the adult hippocampus

Bromodeoxyuridine: a diagnostic tool in biology and medicine, Part III. Proliferation in normal, injured and diseased tissue, growth factors, differentiation, DNA replication sites andin situ hybridization

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