Micronucleus induction by neocarzinostatin and methyl methanesulfonate in ionizing radiation – sensitive Chinese hamster V79 cell mutants

Stopper, Helga; Full, Markus; Helbig, Rainer; Speit, Günter

doi:10.1016/s0921-8777(96)00049-3

Cited by 14 publications

(4 citation statements)

References 20 publications

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“…This type of cell is susceptible to X-radiation, and also exhibits cross-sensitivity to bleomycin and alkylating agents. The results presented are thereby similar to cytogenetic studies where mutant cell lines defective in the repair of double-strand breaks have been shown to have a greater number of spontaneous chromosomal aberrations and a much higher frequency of induced aberrations when compared with wild-type cells, mainly chromatid type aberrations (Stopper et al 1997). Therefore, it was likely genotoxicity that was observed for this cell system in treatments where EMS was present.…”

Section: Discussionsupporting

confidence: 83%

Investigation of Chlorophyllin in CHO-k1 (wild-type) and CHO-xrs5 (repair-deficient) Cells by a Chromosomal Aberration Assay

et al. 2003

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Chlorophyllin, a sodium-copper salt derivative of chlorophyll a and b was evaluated at concentrations of 6.25, 12.5 and 25 mg/ml with regard to its clastogenic and anticlastogenic potential in Chinese hamster ovary cells CHO-k1 (wild-type) and CHO-xrs5 (DNA repair-defective), using a chromosomal aberration test. Cells were subjected to continuous exposure for 12 h to chlorophyllin in the presence or absence of ethyl methane sulfonate (EMS, 310 mg/ml). The results demonstrate that under the experimental conditions utilized, chlorophyllin was not cytotoxic nor clastogenic in either of the cell systems employed. Moreover, anticlastogenic activity was also not observed. Key words Chlorophyllin, CHO cells, Chromosomal aberrations. Currently, there is a growing need to test synthetic and natural chemical compounds, which are in great numbers in our environment, for possible carcinogenicity and mutagenicity. In addition, many substances of plant origin are being investigated with regard to their antimutagenic/anticarcinogenic potential (Mitscher et al. 1992). Therefore, chlorophyllin, a sodium-copper salt derivative of chlorophyll, has been studied for its protective action against the carcinogenic effects of various physical and chemical agents, and how it relates to the mutagenic and clastogenic activity of genotoxic agents. Reported studies suggest that the effects of these compounds correlate with the concentrations used, however without any dose-response type relationship (Romert et al. 1992). Therefore, in view of the ambiguity with respect to the mechanism of action of chlorophylls and their derivatives in the protection against as well as in the induction of DNA damage, the aim of the present study was to evaluate chlorophyllin for clastogenicity and anticlastogenicity in wild-type (k1) and DNA repair-defective (xrs5) CHO cells using a chromosomal aberration test. Materials and methods Cell lines and culture conditions Wild-type Chinese hamster ovary (CHO-k1) cells and a variant line defective in the repair of double-strand DNA (CHO-xrs5), furnished by the Mutagenesis Laboratory of USP-Ribeirão Preto (SP)/Brazil, were grown as monolayers in 25 cm 2 culture flasks. Cells were cultivated in Dulbecco's modified Eagle's medium (DMEM)/Ham's F12, supplemented with 10% fetal bovine serum and 0.1% antibiotic-antimycotic solution, in a BOD chamber at 37°C. Under these conditions, the cell cycle was 12 h.

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Section: Discussionsupporting

confidence: 83%

Investigation of Chlorophyllin in CHO-k1 (wild-type) and CHO-xrs5 (repair-deficient) Cells by a Chromosomal Aberration Assay

et al. 2003

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“…MN formation is related to chromosomal aberration and has been used widely to measure chromosome damage (Matsuoka et al, 1992;Stopper et al, 1997;Fenech, 2002). To investigate whether EBV LMP1 can induce MN formation in human epithelial cells, we examined the micronuclei in RHEK-1 and LMP135 cells in the presence or absence of the DNA-damaging agent bleomycin.…”

Section: Lmp1 Enhances Mn Formationmentioning

confidence: 99%

Epstein–Barr virus latent membrane protein 1 induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells

Liu

Chen

et al. 2004

Oncogene

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The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a viral oncogene and it is essential for the transformation of resting B cells by the virus. The protein acts as a ligand-less membrane receptor and triggers numerous cellular signaling pathways. Cellular transformation frequently has been associated with genomic instability. To investigate whether EBV LMP1 induces chromosomal aberrations, micronucleus (MN) formation was examined in LMP1-expressing epithelial cells. The expression of wild-type LMP1 enhanced both spontaneous and bleomycin-induced MN formation. MN formation may be induced by inactivation of DNA repair and, therefore, we investigated the effect of LMP1 on DNA repair, using a host cell reactivation (HCR) assay. In the HCR assay, LMP1 reduced the capacity for DNA repair of both NPC-TW01 (p53-wild-type) and H1299 (p53-deficient) cells. As reduction of DNA repair by LMP1 occurs in p53-wild-type and p53-deficient cells, it seems that LMP1 can repress DNA repair in a p53-independent manner. Inactivation of DNA repair may render cells sensitive to DNA-damaging agents. In this study, H1299 cells harboring LMP1 were shown to be more sensitive to UV and bleomycin than those with a vector control. Using various deletion mutants of EBV LMP1 to determine the regions of LMP1 required to enhance MN formation, inhibit DNA repair and sensitize cells to DNA-damaging agents, we found that the region a. a. 189-222 (located within the CTAR1 domain) was responsible for sensitizing cells to UV and bleomycin, as well as for enhancing MN formation and repressing DNA repair. Based on these results, we suggest that disruption of DNA repair by LMP-1 results in an accumulation of unrepaired DNA and consequent genomic instability, which may contribute to the oncogenesis of LMP1 in human epithelial cells.

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“…There is some debate and controversy regarding whether cytochalasin B is necessary in continuously cycling cells [21,22]. Furthermore, some studies in which MN induction has been measured after exposure to strong clastogens have indicated that, in certain cell lines with good growth characteristics and optimal culture conditions such that nuclear division occurs, the addition of cytochalasin B is not necessary [23][24][25]. In cycling cells, MN can be scored without cytochalasin B, but it would be difficult to differentiate between dividing and nondividing cells.…”

Section: Rpa Silencing Enhances Ir-induced Micronuclei (Mn) and Apoptmentioning

confidence: 99%

Replication protein A and γ-H2AX foci assembly is triggered by cellular response to DNA double-strand breaks

Balajee

Geard

2004

Experimental Cell Research

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Micronucleus induction by neocarzinostatin and methyl methanesulfonate in ionizing radiation – sensitive Chinese hamster V79 cell mutants

Cited by 14 publications

References 20 publications

Investigation of Chlorophyllin in CHO-k1 (wild-type) and CHO-xrs5 (repair-deficient) Cells by a Chromosomal Aberration Assay

Investigation of Chlorophyllin in CHO-k1 (wild-type) and CHO-xrs5 (repair-deficient) Cells by a Chromosomal Aberration Assay

Epstein–Barr virus latent membrane protein 1 induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells

Replication protein A and γ-H2AX foci assembly is triggered by cellular response to DNA double-strand breaks

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