Sex-specific associations of arsenic exposure with global DNA methylation and hydroxymethylation in leukocytes: results from two studies in Bangladesh.

Abstract

BACKGROUND:

Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)-a class I human carcinogen linked to skin lesion and cancer risk-is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hmC has not been widely studied.

METHODS:

We evaluated associations of As in drinking water, urine, and blood with global %5-mC and %5-hmC in two studies of Bangladeshi adults: (i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity study (n = 196; 49% male, 19-66 years); and (ii) peripheral blood mononuclear cell DNA in the Folate and Oxidative Stress study (n = 375; 49% male, 30-63 years).

RESULTS:

Overall, As was not associated with global %5-mC or %5-hmC. Sex-specific analyses showed that associations of As exposure with global %5-hmC were positive in males and negative in females (P for interaction < 0.01). Analyses examining interactions by elevated plasma total homocysteine (tHcys), an indicator of B-vitamin deficiency, found that tHcys also modified the association between As and global %5-hmC (P for interaction < 0.10).

CONCLUSION:

In two samples, we observed associations between As exposure and global %5-hmC in blood DNA that were modified by sex and tHcys.

IMPACT:

Our findings suggest that As induces sex-specific changes in 5-hmC, an epigenetic mark that has been associated with cancer. Future research should explore whether altered %5-hmC is a mechanism underlying the sex-specific influences of As on skin lesion and cancer outcomes.

• Authors: Megan M Niedzwiecki, Xinhua Liu, Megan N Hall, Tiffany Thomas, Vesna Slavkovich, Vesna Ilievski, Diane Levy, Shafiul Alam, Abu B Siddique, Faruque Parvez, Joseph H Graziano, Mary V Gamble
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 24 Issue 11 Pg. 1748-57 (Nov 2015) ISSN: 1538-7755 [Electronic] United States
• PMID: 26364164 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Drinking Water
• Homocysteine
• 5-hydroxymethylcytosine
• 5-Methylcytosine
• Cytosine
• Arsenic

Topics

• 5-Methylcytosine (analogs & derivatives)
• Adult
• Aged
• Arsenic (adverse effects, blood, urine)
• Bangladesh (epidemiology)
• Cytosine (analogs & derivatives, metabolism)
• DNA Methylation (drug effects)
• Drinking Water (analysis)
• Environmental Exposure (adverse effects, statistics & numerical data)
• Female
• Homocysteine (blood)
• Humans
• Leukocytes (drug effects, metabolism)
• Male
• Middle Aged
• Sex Factors
• Young Adult