Peripheral blood signatures of lead exposure.
Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of part...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3148235?pdf=render |
| _version_ | 1818361476986961920 |
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| author | Heather G LaBreche Sarah K Meadows Joseph R Nevins John P Chute |
| author_facet | Heather G LaBreche Sarah K Meadows Joseph R Nevins John P Chute |
| author_sort | Heather G LaBreche |
| collection | DOAJ |
| description | Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways.Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern.The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. |
| first_indexed | 2024-12-13T21:17:18Z |
| format | Article |
| id | doaj.art-02cbd5642ec94d7585ac30e81de1c808 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:17:18Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-02cbd5642ec94d7585ac30e81de1c8082022-12-21T23:31:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2304310.1371/journal.pone.0023043Peripheral blood signatures of lead exposure.Heather G LaBrecheSarah K MeadowsJoseph R NevinsJohn P ChuteCurrent evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways.Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern.The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway.http://europepmc.org/articles/PMC3148235?pdf=render |
| spellingShingle | Heather G LaBreche Sarah K Meadows Joseph R Nevins John P Chute Peripheral blood signatures of lead exposure. PLoS ONE |
| title | Peripheral blood signatures of lead exposure. |
| title_full | Peripheral blood signatures of lead exposure. |
| title_fullStr | Peripheral blood signatures of lead exposure. |
| title_full_unstemmed | Peripheral blood signatures of lead exposure. |
| title_short | Peripheral blood signatures of lead exposure. |
| title_sort | peripheral blood signatures of lead exposure |
| url | http://europepmc.org/articles/PMC3148235?pdf=render |
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