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Effects of folate on telomere length and chromosome stability of human fibroblasts and melanoma cells in vitro: a comparison of folic acid and 5-methyltetrahydrofolate
Abstract Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 v...
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| Published in: | Mutagenesis 2023-05, Vol.38 (2), p.100-108 |
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| container_end_page | 108 |
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| container_title | Mutagenesis |
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| creator | Wang, Han Ni, Juan Guo, Xihan Xue, Jinglun Wang, Xu |
| description | Abstract
Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA- and 5-MeTHF-deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression, and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF. |
| doi_str_mv | 10.1093/mutage/gead004 |
| format | article |
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Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA- and 5-MeTHF-deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression, and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF.</description><identifier>ISSN: 0267-8357</identifier><identifier>EISSN: 1464-3804</identifier><identifier>DOI: 10.1093/mutage/gead004</identifier><identifier>PMID: 36932659</identifier><language>eng</language><publisher>UK: Oxford University Press</publisher><subject>Chromosomal Instability ; Fibroblasts - metabolism ; Folic Acid - pharmacology ; Humans ; Melanoma ; Telomerase - genetics ; Telomerase - metabolism ; Telomere - metabolism</subject><ispartof>Mutagenesis, 2023-05, Vol.38 (2), p.100-108</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c284t-9d003f6f5077248b935d9a2def21edfe9e94ff23eeb65f260befede5831957123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36932659$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Han</creatorcontrib><creatorcontrib>Ni, Juan</creatorcontrib><creatorcontrib>Guo, Xihan</creatorcontrib><creatorcontrib>Xue, Jinglun</creatorcontrib><creatorcontrib>Wang, Xu</creatorcontrib><title>Effects of folate on telomere length and chromosome stability of human fibroblasts and melanoma cells in vitro: a comparison of folic acid and 5-methyltetrahydrofolate</title><title>Mutagenesis</title><addtitle>Mutagenesis</addtitle><description>Abstract
Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA- and 5-MeTHF-deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression, and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF.</description><subject>Chromosomal Instability</subject><subject>Fibroblasts - metabolism</subject><subject>Folic Acid - pharmacology</subject><subject>Humans</subject><subject>Melanoma</subject><subject>Telomerase - genetics</subject><subject>Telomerase - metabolism</subject><subject>Telomere - metabolism</subject><issn>0267-8357</issn><issn>1464-3804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNqFkUtr3DAUhUVpaCaPbZdFy2bhRA_LtrIrIW0CgWzatZGtq7GKZE0kuTC_KH8zmnrabVYXLt8593EQ-kzJNSWS3_glqy3cbEFpQuoPaEPrpq54R-qPaENY01YdF-0pOkvpNyG0ZQ35hE55IzlrhNyg13tjYMwJB4NNcCoDDjPO4IKHCNjBvM0TVrPG4xSDD6n0ccpqsM7m_UE1LV7N2NghhsGpVKwOtAen5uAVHsG5hO2M_9gcwy0uneB3KtpU5qxD7YjVaPVfnag85GnvMuSopr2OYd3qAp0Y5RJcHus5-vX9_ufdQ_X0_OPx7ttTNbKuzpUsX-CmMYK0Lau7QXKhpWIaDKOgDUiQtTGMAwyNMOUZAxjQIDpOpWgp4-fo6-q7i-FlgZR7b9PhBjVDWFLPOsqF6LqWFPR6RccYUopg-l20XsV9T0l_CKdfw-mP4RTBl6P3MnjQ__F_aRTgagXCsnvP7A2sF5-T</recordid><startdate>20230512</startdate><enddate>20230512</enddate><creator>Wang, Han</creator><creator>Ni, Juan</creator><creator>Guo, Xihan</creator><creator>Xue, Jinglun</creator><creator>Wang, Xu</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20230512</creationdate><title>Effects of folate on telomere length and chromosome stability of human fibroblasts and melanoma cells in vitro: a comparison of folic acid and 5-methyltetrahydrofolate</title><author>Wang, Han ; Ni, Juan ; Guo, Xihan ; Xue, Jinglun ; Wang, Xu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c284t-9d003f6f5077248b935d9a2def21edfe9e94ff23eeb65f260befede5831957123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Chromosomal Instability</topic><topic>Fibroblasts - metabolism</topic><topic>Folic Acid - pharmacology</topic><topic>Humans</topic><topic>Melanoma</topic><topic>Telomerase - genetics</topic><topic>Telomerase - metabolism</topic><topic>Telomere - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Han</creatorcontrib><creatorcontrib>Ni, Juan</creatorcontrib><creatorcontrib>Guo, Xihan</creatorcontrib><creatorcontrib>Xue, Jinglun</creatorcontrib><creatorcontrib>Wang, Xu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Mutagenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Han</au><au>Ni, Juan</au><au>Guo, Xihan</au><au>Xue, Jinglun</au><au>Wang, Xu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of folate on telomere length and chromosome stability of human fibroblasts and melanoma cells in vitro: a comparison of folic acid and 5-methyltetrahydrofolate</atitle><jtitle>Mutagenesis</jtitle><addtitle>Mutagenesis</addtitle><date>2023-05-12</date><risdate>2023</risdate><volume>38</volume><issue>2</issue><spage>100</spage><epage>108</epage><pages>100-108</pages><issn>0267-8357</issn><eissn>1464-3804</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Abstract
Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA- and 5-MeTHF-deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression, and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF.</abstract><cop>UK</cop><pub>Oxford University Press</pub><pmid>36932659</pmid><doi>10.1093/mutage/gead004</doi><tpages>9</tpages></addata></record> |
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| subjects | Chromosomal Instability Fibroblasts - metabolism Folic Acid - pharmacology Humans Melanoma Telomerase - genetics Telomerase - metabolism Telomere - metabolism |
| title | Effects of folate on telomere length and chromosome stability of human fibroblasts and melanoma cells in vitro: a comparison of folic acid and 5-methyltetrahydrofolate |
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