Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study
<p>Abstract</p> <p>Exposure to ambient air particles matter (PM) has been associated with increased risk of lung cancer. Aberrant tumor suppressor gene promoter methylation has emerged as a promising biomarker for cancers, including lung cancer. Whether exposure to PM is associated...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2011-08-01
|
Series: | Particle and Fibre Toxicology |
Online Access: | http://www.particleandfibretoxicology.com/content/8/1/25 |
_version_ | 1818564988558639104 |
---|---|
author | Cantone Laura Rizzo Giovanna Marinelli Barbara Angelici Laura Bonzini Matteo Nordio Francesco Tarantini Letizia Zhang Xiao Hou Lifang Apostoli Pietro Bertazzi Pier Baccarelli Andrea |
author_facet | Cantone Laura Rizzo Giovanna Marinelli Barbara Angelici Laura Bonzini Matteo Nordio Francesco Tarantini Letizia Zhang Xiao Hou Lifang Apostoli Pietro Bertazzi Pier Baccarelli Andrea |
author_sort | Cantone Laura |
collection | DOAJ |
description | <p>Abstract</p> <p>Exposure to ambient air particles matter (PM) has been associated with increased risk of lung cancer. Aberrant tumor suppressor gene promoter methylation has emerged as a promising biomarker for cancers, including lung cancer. Whether exposure to PM is associated with peripheral blood leukocyte (PBL) DNA methylation in tumor suppressor genes has not been evaluated. In 63 male healthy steel workers with well-characterized exposure to metal-rich particles nearby Brescia, Italy, we evaluated whether exposure to PM and metal components was associated with PBL DNA methylation in 4 tumor suppressor genes (i.e., APC, p16, p53 and RASSF1A). Blood samples were obtained on the 1<sup>st </sup>(baseline) and 4<sup>th </sup>day (post-exposure) of the same work week and DNA methylation was measured using pyrosequencing. A linear mixed model was used to examine the correlations of the exposure with promoter methylation levels. Mean promoter DNA methylation levels of APC or p16 were significantly higher in post-exposure samples compared to that in baseline samples (p-values = 0.005 for APC, and p-value = 0.006 for p16). By contrast, the mean levels of p53 or RASSF1A promoter methylation was decreased in post-exposure samples compared to that in baseline samples (p-value = 0.015 for p53; and p-value < 0.001 for RASSF1A). In post-exposure samples, APC methylation was positively associated with PM<sub>10 </sub>(β = 0.27, 95% CI: 0.13-0.40), and PM<sub>1 </sub>(β = 0.23, 95% CI: 0.09-0.38). In summary, ambient PM exposure was associated with PBL DNA methylation levels of tumor suppressor genes of APC, p16, p53 and RASSF1A, suggesting that such methylation alterations may reflect processes related to PM-induced lung carcinogenesis.</p> |
first_indexed | 2024-12-14T01:35:35Z |
format | Article |
id | doaj.art-5167de9506374ce98d31133ef793264f |
institution | Directory Open Access Journal |
issn | 1743-8977 |
language | English |
last_indexed | 2024-12-14T01:35:35Z |
publishDate | 2011-08-01 |
publisher | BMC |
record_format | Article |
series | Particle and Fibre Toxicology |
spelling | doaj.art-5167de9506374ce98d31133ef793264f2022-12-21T23:21:53ZengBMCParticle and Fibre Toxicology1743-89772011-08-01812510.1186/1743-8977-8-25Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional studyCantone LauraRizzo GiovannaMarinelli BarbaraAngelici LauraBonzini MatteoNordio FrancescoTarantini LetiziaZhang XiaoHou LifangApostoli PietroBertazzi PierBaccarelli Andrea<p>Abstract</p> <p>Exposure to ambient air particles matter (PM) has been associated with increased risk of lung cancer. Aberrant tumor suppressor gene promoter methylation has emerged as a promising biomarker for cancers, including lung cancer. Whether exposure to PM is associated with peripheral blood leukocyte (PBL) DNA methylation in tumor suppressor genes has not been evaluated. In 63 male healthy steel workers with well-characterized exposure to metal-rich particles nearby Brescia, Italy, we evaluated whether exposure to PM and metal components was associated with PBL DNA methylation in 4 tumor suppressor genes (i.e., APC, p16, p53 and RASSF1A). Blood samples were obtained on the 1<sup>st </sup>(baseline) and 4<sup>th </sup>day (post-exposure) of the same work week and DNA methylation was measured using pyrosequencing. A linear mixed model was used to examine the correlations of the exposure with promoter methylation levels. Mean promoter DNA methylation levels of APC or p16 were significantly higher in post-exposure samples compared to that in baseline samples (p-values = 0.005 for APC, and p-value = 0.006 for p16). By contrast, the mean levels of p53 or RASSF1A promoter methylation was decreased in post-exposure samples compared to that in baseline samples (p-value = 0.015 for p53; and p-value < 0.001 for RASSF1A). In post-exposure samples, APC methylation was positively associated with PM<sub>10 </sub>(β = 0.27, 95% CI: 0.13-0.40), and PM<sub>1 </sub>(β = 0.23, 95% CI: 0.09-0.38). In summary, ambient PM exposure was associated with PBL DNA methylation levels of tumor suppressor genes of APC, p16, p53 and RASSF1A, suggesting that such methylation alterations may reflect processes related to PM-induced lung carcinogenesis.</p>http://www.particleandfibretoxicology.com/content/8/1/25 |
spellingShingle | Cantone Laura Rizzo Giovanna Marinelli Barbara Angelici Laura Bonzini Matteo Nordio Francesco Tarantini Letizia Zhang Xiao Hou Lifang Apostoli Pietro Bertazzi Pier Baccarelli Andrea Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study Particle and Fibre Toxicology |
title | Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study |
title_full | Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study |
title_fullStr | Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study |
title_full_unstemmed | Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study |
title_short | Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study |
title_sort | ambient pm exposure and dna methylation in tumor suppressor genes a cross sectional study |
url | http://www.particleandfibretoxicology.com/content/8/1/25 |
work_keys_str_mv | AT cantonelaura ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT rizzogiovanna ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT marinellibarbara ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT angelicilaura ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT bonzinimatteo ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT nordiofrancesco ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT tarantiniletizia ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT zhangxiao ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT houlifang ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT apostolipietro ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT bertazzipier ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy AT baccarelliandrea ambientpmexposureanddnamethylationintumorsuppressorgenesacrosssectionalstudy |