caa a22 4500 445852682 CHVBK 20180317145418.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00204-010-0611-z doi (NATIONALLICENCE)springer-10.1007/s00204-010-0611-z Global DNA methylation in the mouse liver is affected by methyl deficiency and arsenic in a sex-dependent manner [Elektronische Daten] [Keiko Nohara, Takashi Baba, Hikari Murai, Yayoi Kobayashi, Takehiro Suzuki, Yukiyo Tateishi, Michiyo Matsumoto, Noriko Nishimura, Tomoharu Sano] Arsenic, a carcinogen, is assumed to induce global DNA hypomethylation by consuming the universal methyl donor S-adenosylmethionine (SAM) in the body. A previous study reported that a methyl-deficient diet (MDD) with arsenic intake greatly reduced global DNA methylation (the content of 5-methylcytosine) in the liver of male C57BL/6 mice. In the present study, we investigated the DNA methylation level, SAM content, and expression of DNA methyltransferases (DNMTs) in the liver of male and female C57BL/6 mice fed a methyl-sufficient diet (MSD), an MDD, or an MDD+arsenic. The DNA methylation level was accurately determined by measuring the content of genomic 5-methyldeoxycytidine (5medC) by high-performance liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) using stable-isotope-labeled 5medC and deoxycytidine (dC) as internal standards. The results of this study revealed that while the MDD and arsenic tended to reduce the genomic 5meC content in the male mice livers, the MDD+arsenic significantly increased the 5meC content in the female mice livers. Another unexpected finding was the small differences in 5meC content among the groups. The MDD and MDD+arsenic suppressed DNMT1 expression only in the male mice livers. In contrast, SAM content was reduced by the MDD and MDD+arsenic only in the livers of female mice, showing that the changes in 5meC content were not attributable to SAM content. The sex-dependent changes in 5meC content induced by methyl deficiency and arsenic may be involved in differences in male and female susceptibility to diseases via epigenetic modification of physiological functions. Springer-Verlag, 2010 DNA methylation nationallicence Methyl deficiency nationallicence Arsenic nationallicence 5-Methylcytosine nationallicence S-adenosylmethionine nationallicence Sex dependence nationallicence Nohara Keiko Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Baba Takashi Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Murai Hikari Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Kobayashi Yayoi Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Suzuki Takehiro Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Tateishi Yukiyo Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Matsumoto Michiyo Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Nishimura Noriko Research Center for Environmental Risk, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Sano Tomoharu Laboratory of Intellectual Fundamentals for Environmental Studies, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 653-661 0340-5761 85:6<653 2011 85 204 https://doi.org/10.1007/s00204-010-0611-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0611-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nohara Keiko Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 700 1- Baba Takashi Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 700 1- Murai Hikari Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 700 1- Kobayashi Yayoi Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 700 1- Suzuki Takehiro Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 700 1- Tateishi Yukiyo Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 700 1- Matsumoto Michiyo Environmental Health Sciences Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 700 1- Nishimura Noriko Research Center for Environmental Risk, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 700 1- Sano Tomoharu Laboratory of Intellectual Fundamentals for Environmental Studies, National Institute for Environmental Studies, 305-8506, Tsukuba, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 653-661 0340-5761 85:6<653 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer