Dioxin induces genomic instability in mouse embryonic fibroblasts.
Ionizing radiation and certain other exposures have been shown to induce genomic instability (GI), i.e., delayed genetic damage observed many cell generations later in the progeny of the exposed cells. The aim of this study was to investigate induction of GI by a nongenotoxic carcinogen, 2,3,7,8-tet...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3362596?pdf=render |
| _version_ | 1818281996017729536 |
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| author | Merja Korkalainen Katriina Huumonen Jonne Naarala Matti Viluksela Jukka Juutilainen |
| author_facet | Merja Korkalainen Katriina Huumonen Jonne Naarala Matti Viluksela Jukka Juutilainen |
| author_sort | Merja Korkalainen |
| collection | DOAJ |
| description | Ionizing radiation and certain other exposures have been shown to induce genomic instability (GI), i.e., delayed genetic damage observed many cell generations later in the progeny of the exposed cells. The aim of this study was to investigate induction of GI by a nongenotoxic carcinogen, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mouse embryonic fibroblasts (C3H10T1/2) were exposed to 1, 10 or 100 nM TCDD for 2 days. Micronuclei (MN) and expression of selected cancer-related genes were assayed both immediately and at a delayed point in time (8 days). For comparison, similar experiments were done with cadmium, a known genotoxic agent. TCDD treatment induced an elevated frequency of MN at 8 days, but not directly after the exposure. TCDD-induced alterations in gene expression were also mostly delayed, with more changes observed at 8 days than at 2 days. Exposure to cadmium produced an opposite pattern of responses, with pronounced effects immediately after exposure but no increase in MN and few gene expression changes at 8 days. Although all responses to TCDD alone were delayed, menadione-induced DNA damage (measured by the Comet assay), was found to be increased directly after a 2-day TCDD exposure, indicating that the stability of the genome was compromised already at this time point. The results suggested a flat dose-response relationship consistent with dose-response data reported for radiation-induced GI. These findings indicate that TCDD, although not directly genotoxic, induces GI, which is associated with impaired DNA damage response. |
| first_indexed | 2024-12-13T00:13:59Z |
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| id | doaj.art-47c1fd7cc10345478a2eb47996657df3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T00:13:59Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-47c1fd7cc10345478a2eb47996657df32022-12-22T00:05:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3789510.1371/journal.pone.0037895Dioxin induces genomic instability in mouse embryonic fibroblasts.Merja KorkalainenKatriina HuumonenJonne NaaralaMatti VilukselaJukka JuutilainenIonizing radiation and certain other exposures have been shown to induce genomic instability (GI), i.e., delayed genetic damage observed many cell generations later in the progeny of the exposed cells. The aim of this study was to investigate induction of GI by a nongenotoxic carcinogen, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mouse embryonic fibroblasts (C3H10T1/2) were exposed to 1, 10 or 100 nM TCDD for 2 days. Micronuclei (MN) and expression of selected cancer-related genes were assayed both immediately and at a delayed point in time (8 days). For comparison, similar experiments were done with cadmium, a known genotoxic agent. TCDD treatment induced an elevated frequency of MN at 8 days, but not directly after the exposure. TCDD-induced alterations in gene expression were also mostly delayed, with more changes observed at 8 days than at 2 days. Exposure to cadmium produced an opposite pattern of responses, with pronounced effects immediately after exposure but no increase in MN and few gene expression changes at 8 days. Although all responses to TCDD alone were delayed, menadione-induced DNA damage (measured by the Comet assay), was found to be increased directly after a 2-day TCDD exposure, indicating that the stability of the genome was compromised already at this time point. The results suggested a flat dose-response relationship consistent with dose-response data reported for radiation-induced GI. These findings indicate that TCDD, although not directly genotoxic, induces GI, which is associated with impaired DNA damage response.http://europepmc.org/articles/PMC3362596?pdf=render |
| spellingShingle | Merja Korkalainen Katriina Huumonen Jonne Naarala Matti Viluksela Jukka Juutilainen Dioxin induces genomic instability in mouse embryonic fibroblasts. PLoS ONE |
| title | Dioxin induces genomic instability in mouse embryonic fibroblasts. |
| title_full | Dioxin induces genomic instability in mouse embryonic fibroblasts. |
| title_fullStr | Dioxin induces genomic instability in mouse embryonic fibroblasts. |
| title_full_unstemmed | Dioxin induces genomic instability in mouse embryonic fibroblasts. |
| title_short | Dioxin induces genomic instability in mouse embryonic fibroblasts. |
| title_sort | dioxin induces genomic instability in mouse embryonic fibroblasts |
| url | http://europepmc.org/articles/PMC3362596?pdf=render |
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