Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents
Caffeine has been previously reported to enhance the lethal potential of many DNA-damaging agents in rodent cells 1–5 . This effect has most commonly been ascribed to the binding of caffeine to single-stranded DNA 6 , and the resulting inhibition of post-replication repair 7–10 , which is associated...
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| Veröffentlicht in: | Nature (London) 1980-05, Vol.285 (5763), p.326-329 |
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| creator | Murnane, John P Byfield, John E Ward, John F Calabro-Jones, Paula |
| description | Caffeine has been previously reported to enhance the lethal potential of many DNA-damaging agents in rodent cells
1–5
. This effect has most commonly been ascribed to the binding of caffeine to single-stranded DNA
6
, and the resulting inhibition of post-replication repair
7–10
, which is associated with the synthesis of abnormally small nascent DNA fragments
7,11–13
. However, certain aspects of this theory remain unclear: (1) why does the addition of caffeine to damaged cells elevate the level of DNA synthesis when it supposedly blocks post-replication repair
10,14
, and (2) as pointed out by Cleaver
15
, why does caffeine continue to exert its synergistic lethal effects until completion of the S phase
16,17
, even though the size of newly synthesized DNA seems normal much earlier
18–20
? The present studies with nitrogen mustard (HN
2
) fail to demonstrate any effect of non-lethal concentrations of methylated xanthines (MXs) on removal of DNA damage or post-replication repair in conditions producing synergistic lethal effects. We demonstrate an influence by MXs on initiation of DNA synthesis in damaged replicons, and propose that this effect is primarily responsible for the synergistic lethal properties of these drugs. |
| doi_str_mv | 10.1038/285326a0 |
| format | Article |
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1–5
. This effect has most commonly been ascribed to the binding of caffeine to single-stranded DNA
6
, and the resulting inhibition of post-replication repair
7–10
, which is associated with the synthesis of abnormally small nascent DNA fragments
7,11–13
. However, certain aspects of this theory remain unclear: (1) why does the addition of caffeine to damaged cells elevate the level of DNA synthesis when it supposedly blocks post-replication repair
10,14
, and (2) as pointed out by Cleaver
15
, why does caffeine continue to exert its synergistic lethal effects until completion of the S phase
16,17
, even though the size of newly synthesized DNA seems normal much earlier
18–20
? The present studies with nitrogen mustard (HN
2
) fail to demonstrate any effect of non-lethal concentrations of methylated xanthines (MXs) on removal of DNA damage or post-replication repair in conditions producing synergistic lethal effects. We demonstrate an influence by MXs on initiation of DNA synthesis in damaged replicons, and propose that this effect is primarily responsible for the synergistic lethal properties of these drugs.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/285326a0</identifier><identifier>PMID: 7374784</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Caffeine - pharmacology ; Cell Line ; Cell Survival - drug effects ; DNA Repair - drug effects ; DNA Replication - drug effects ; Drug Interactions ; Humanities and Social Sciences ; Humans ; letter ; Mechlorethamine - pharmacology ; Mice ; Molecular Weight ; multidisciplinary ; Replicon - drug effects ; Science ; Science (multidisciplinary)</subject><ispartof>Nature (London), 1980-05, Vol.285 (5763), p.326-329</ispartof><rights>Springer Nature Limited 1980</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c364t-792f476d62594043431e72379266791a48ab930b49f119654e203bfefac810023</citedby><cites>FETCH-LOGICAL-c364t-792f476d62594043431e72379266791a48ab930b49f119654e203bfefac810023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/285326a0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/285326a0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7374784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Murnane, John P</creatorcontrib><creatorcontrib>Byfield, John E</creatorcontrib><creatorcontrib>Ward, John F</creatorcontrib><creatorcontrib>Calabro-Jones, Paula</creatorcontrib><title>Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Caffeine has been previously reported to enhance the lethal potential of many DNA-damaging agents in rodent cells
1–5
. This effect has most commonly been ascribed to the binding of caffeine to single-stranded DNA
6
, and the resulting inhibition of post-replication repair
7–10
, which is associated with the synthesis of abnormally small nascent DNA fragments
7,11–13
. However, certain aspects of this theory remain unclear: (1) why does the addition of caffeine to damaged cells elevate the level of DNA synthesis when it supposedly blocks post-replication repair
10,14
, and (2) as pointed out by Cleaver
15
, why does caffeine continue to exert its synergistic lethal effects until completion of the S phase
16,17
, even though the size of newly synthesized DNA seems normal much earlier
18–20
? The present studies with nitrogen mustard (HN
2
) fail to demonstrate any effect of non-lethal concentrations of methylated xanthines (MXs) on removal of DNA damage or post-replication repair in conditions producing synergistic lethal effects. We demonstrate an influence by MXs on initiation of DNA synthesis in damaged replicons, and propose that this effect is primarily responsible for the synergistic lethal properties of these drugs.</description><subject>Animals</subject><subject>Caffeine - pharmacology</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>DNA Repair - drug effects</subject><subject>DNA Replication - drug effects</subject><subject>Drug Interactions</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>letter</subject><subject>Mechlorethamine - pharmacology</subject><subject>Mice</subject><subject>Molecular Weight</subject><subject>multidisciplinary</subject><subject>Replicon - drug effects</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1980</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkM1OwzAQhC0EKqUg8QIgH-EQsGPHdo6oKj9SJS5wJXLSdZuSOJXtCPr2uKT0xGmlmU-jnUHokpI7Spi6T1XGUqHJERpTLkXChZLHaExIqhKimDhFZ96vCSEZlXyERpJJLhUfo4-ZMVAFjzuDWwirbaMDLPC3tmFVW4i6xa1uW93U2uIKmsbj4OAX-qrDCpe16W0V6s7qBuvmcxdQ2yXWS7DBn6MToxsPF_s7Qe-Ps7fpczJ_fXqZPsyTigkeEpmnJr69EGmWc8IZZxRkyqIshMyp5kqXOSMlzw2lucg4pISVBoyuFI0l2QTdDLmV67x3YIqNq1vttgUlxW6h4m-hiF4N6KYvW1gcwP0k0b8dfB8duwRXrLvexXb-v6zrgbU69A4OWQfgB6mjd58</recordid><startdate>19800529</startdate><enddate>19800529</enddate><creator>Murnane, John P</creator><creator>Byfield, John E</creator><creator>Ward, John F</creator><creator>Calabro-Jones, Paula</creator><general>Nature Publishing Group UK</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></search><sort><creationdate>19800529</creationdate><title>Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents</title><author>Murnane, John P ; Byfield, John E ; Ward, John F ; Calabro-Jones, Paula</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c364t-792f476d62594043431e72379266791a48ab930b49f119654e203bfefac810023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1980</creationdate><topic>Animals</topic><topic>Caffeine - pharmacology</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>DNA Repair - drug effects</topic><topic>DNA Replication - drug effects</topic><topic>Drug Interactions</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>letter</topic><topic>Mechlorethamine - pharmacology</topic><topic>Mice</topic><topic>Molecular Weight</topic><topic>multidisciplinary</topic><topic>Replicon - drug effects</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murnane, John P</creatorcontrib><creatorcontrib>Byfield, John E</creatorcontrib><creatorcontrib>Ward, John F</creatorcontrib><creatorcontrib>Calabro-Jones, Paula</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Murnane, John P</au><au>Byfield, John E</au><au>Ward, John F</au><au>Calabro-Jones, Paula</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>1980-05-29</date><risdate>1980</risdate><volume>285</volume><issue>5763</issue><spage>326</spage><epage>329</epage><pages>326-329</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><abstract>Caffeine has been previously reported to enhance the lethal potential of many DNA-damaging agents in rodent cells
1–5
. This effect has most commonly been ascribed to the binding of caffeine to single-stranded DNA
6
, and the resulting inhibition of post-replication repair
7–10
, which is associated with the synthesis of abnormally small nascent DNA fragments
7,11–13
. However, certain aspects of this theory remain unclear: (1) why does the addition of caffeine to damaged cells elevate the level of DNA synthesis when it supposedly blocks post-replication repair
10,14
, and (2) as pointed out by Cleaver
15
, why does caffeine continue to exert its synergistic lethal effects until completion of the S phase
16,17
, even though the size of newly synthesized DNA seems normal much earlier
18–20
? The present studies with nitrogen mustard (HN
2
) fail to demonstrate any effect of non-lethal concentrations of methylated xanthines (MXs) on removal of DNA damage or post-replication repair in conditions producing synergistic lethal effects. We demonstrate an influence by MXs on initiation of DNA synthesis in damaged replicons, and propose that this effect is primarily responsible for the synergistic lethal properties of these drugs.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>7374784</pmid><doi>10.1038/285326a0</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 1980-05, Vol.285 (5763), p.326-329 |
| issn | 0028-0836 1476-4687 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals; Nature |
| subjects | Animals Caffeine - pharmacology Cell Line Cell Survival - drug effects DNA Repair - drug effects DNA Replication - drug effects Drug Interactions Humanities and Social Sciences Humans letter Mechlorethamine - pharmacology Mice Molecular Weight multidisciplinary Replicon - drug effects Science Science (multidisciplinary) |
| title | Effects of methylated xanthines on mammalian cells treated with bifunctional alkylating agents |
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