Comparative induction of micronuclei in repair-deficient and -proficient Chinese hamster cell lines following clastogen or aneugen exposures

Hermine, Thierry; Jones, Nigel J.; Parry, James M.

doi:10.1016/s0165-1218(97)00053-0

Cited by 18 publications

(8 citation statements)

References 32 publications

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“…In the VP-16 group, a total of 208 MN were analyzed by FISH and 83 MN (39.9%) were signal-positive. This result is similar to findings obtained by CREST-staining of VP-16-induced MN in Chinese hamster cells [Hermine et al, 1997] and contrasts with data from neonatal human lymphocytes [Slavotinek et al, 1993] and the human lymphoblastoid cell line TK6 [Wang and Eastmond, 2002] (Table II), 59.0% had one signal, 31.3% contained two signals, and 9.6% had Ն3 signals. This distribution indicates that more than half of the signal-positive MN were formed by a single lagging chromosome and the rest of the signal-positive MN contained several lagging chromosomes or nondisjoined chromatids.…”

Section: Resultssupporting

confidence: 86%

Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probe

Attia

Kliesch

Schriever‐Schwemmer

et al. 2003

Environ and Mol Mutagen

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The topoisomerase II (topo II) inhibitors etoposide (VP-16) and merbarone (MER) were investigated with the in vivo micronucleus test (MN test) combined with fluorescence in situ hybridization (FISH) using the mouse minor satellite DNA probe to discriminate MN of clastogenic and aneugenic origin. All experiments were performed with male (102/ElxC3H/El) F1 mice bred in the mouse colony of the GSF Research Center. The sample size per experimental group was five animals and 2,000 polychromatic erythrocytes (PCE) were scored per animal from coded slides in the conventional MN test. A separate set of coded slides was used for the FISH analysis. All treatments consisted of single intraperitoneal injections. Colchicine (COL, 3 mg/kg) and mitomycin (MMC, 1 mg/kg) were used as a positive control aneugen and clastogen, respectively, and these compounds produced the expected responses. A dose of 1 mg/kg VP-16 induced 3.44% MNPCE (compared to the concurrent solvent control of 0.37%, P < 0.001) and of these 39.9% (1.4% MNPCE) showed one or more fluorescent signals. MER (7.5-60 mg/kg) increased the MNPCE frequencies in a dose-dependent manner, with 15 mg/kg being the lowest positive dose. At the highest dose of 60 mg/kg of MER, a total of 4.26% MNPCE were found (compared to 0.31% in the concurrent solvent control, P < 0.001) and of these 46.2% (2.0% MNPCE) contained one or more fluorescent signals. The data demonstrate that VP-16 and MER induced both clastogenic and aneugenic events despite their different modes of topo II inhibition.

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Section: Resultssupporting

confidence: 86%

Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probe

Attia

Kliesch

Schriever‐Schwemmer

et al. 2003

Environ and Mol Mutagen

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“…Etoposide induces DNA strand breaks by inhibiting the ligation function of DNA topoisomerase II [Hande, 1998]. Etoposide is a mutagen in vitro and a clastogen in vivo [Sjoblom et al, 1994;Garriott et al, 1995;Hermine et al, 1997;Boos and Stopper, 2000].…”

Section: Discussionmentioning

confidence: 99%

Mutagenicity of γ‐radiation, mitomycin C, and etoposide in the Hprt and Tk genes of Tk^+/− mice†

Dobrovolsky

Shaddock

Heflich

2002

Environ and Mol Mutagen

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The recently developed Tk(+/-) mouse detects in vivo somatic cell mutation in the endogenous, autosomal Tk gene. To evaluate the sensitivity of this model, we have treated Tk(+/-) mice with three agents that induce DNA damage by different mechanisms, and determined spleen lymphocyte mutant frequencies (MFs) in the autosomal Tk gene and in the X-linked Hprt gene. gamma-Radiation, which produces single- and double-strand breaks by nonspecific oxidative stress, efficiently increased Hprt MF, but not Tk MF. Mitomycin C, which produces bulky DNA monoadducts and crosslinks, was mutagenic in both the Hprt and Tk genes, but the response was greater in the Tk gene. An inhibitor of the ligase function of DNA topoisomerase II, etoposide, did not increase Hprt MF, and induced a small, but nonsignificant increase in Tk MF. Combined with previous data, the results indicate that the two genes are differentially sensitive to many agents, and that the Tk gene is more sensitive than the Hprt gene to some, but not all types of DNA damage.

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“…The induction of micronuclei has for long been recognized as a consequent of radiotherapy as well as genotoxic chemotherapeutics [158][159][160]. Treatment-induced micronuclei formation has been linked to adaptation to a G2/M cell cycle arrest.…”

Section: Tumor-promoting Features Of Cgas/sting Signalingmentioning

confidence: 99%

Inflammatory signaling in genomically instable cancers

Talens

Vugt

2019

Cell Cycle

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Recent studies have shown that genomic instability in tumor cells leads to activation of inflammatory signaling through the cGAS/STING pathway. In this review, we describe multiple ways by which genomic instability leads to cGAS/STING-mediated inflammatory signaling, as well as the consequences for tumor development and the tumor microenvironment. Also, we elaborate on how tumor cells have apparently evolved to escape the immune surveillance mechanisms that are triggered by cGAS/STING signaling. Finally, we describe how cGAS/STING-mediated inflammatory signaling can be therapeutically targeted to improve therapy responses.

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Comparative induction of micronuclei in repair-deficient and -proficient Chinese hamster cell lines following clastogen or aneugen exposures

Cited by 18 publications

References 32 publications

Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probe

Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probe

Mutagenicity of γ‐radiation, mitomycin C, and etoposide in the Hprt and Tk genes of Tk^+/− mice†

Inflammatory signaling in genomically instable cancers

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Comparative induction of micronuclei in repair-deficient and -proficient Chinese hamster cell lines following clastogen or aneugen exposures

Cited by 18 publications

References 32 publications

Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probe

Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probe

Mutagenicity of γ‐radiation, mitomycin C, and etoposide in the Hprt and Tk genes of Tk+/− mice†

Inflammatory signaling in genomically instable cancers

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Product

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Mutagenicity of γ‐radiation, mitomycin C, and etoposide in the Hprt and Tk genes of Tk^+/− mice†