Limited proliferation of stem cells surviving alkylating agents View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1976-07

AUTHORS

LESLIE E. BOTNICK, EILEEN C. HANNON, SAMUEL HELLMAN

ABSTRACT

HAYFLICK observed that when human foetal tissue was cultivated in vitro the cells underwent 50±10 population doublings before death1. Whether this phenomenon is a property of all diploid cells in culture and is pertinent to cell renewal systems in vivo has been the subject of much discussion. Haematopoietic failure is rarely the cause of death in animal or man, presumably because this cell renewal system has a proliferative capacity which is either unlimited or, if limited, exceeds the life span of a normal animal. The proliferative capacity of the haematopoietic system, if restricted, might become exhausted when stressed by the prolonged use of cytotoxic agents. In these circumstances, significant stem cell division would be necessary to return to the steady state, thereby using much of the stem cell proliferative capacity. We have carried out experiments in mice attempting to simulate the clinical use of chemotherapeutic agents that might result in exhausting the proliferative capacity of haematopoietic stem cells. Two alkylating agents, Busulfan and L-phenylalanine (L-Pam) were investigated. Mice treated with Busulfan and to a lesser extent L-Pam demonstrate permanent damage to the proliferative capacity of surviving stem cells as measured by serial transplantation. Such data may have relevance to the use of these agents in the clinic where there is great interest in such agents to destroy presumed subclinical micrometastases in patients expected to have extended survival. More... »

PAGES

68-70

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/262068a0

DOI

http://dx.doi.org/10.1038/262068a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053161644

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/934328


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1102", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Cardiorespiratory Medicine and Haematology", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Animals", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Bone Marrow", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Bone Marrow Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Busulfan", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Division", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hematopoietic Stem Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mice, Inbred C3H", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Phenylalanine", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Harvard Medical School, Joint Center for Radiation Therapy, 50 Binney Street, 02115, Boston, Massachusetts", 
          "id": "http://www.grid.ac/institutes/grid.38142.3c", 
          "name": [
            "Harvard Medical School, Joint Center for Radiation Therapy, 50 Binney Street, 02115, Boston, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "BOTNICK", 
        "givenName": "LESLIE E.", 
        "id": "sg:person.074622136.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.074622136.37"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Harvard Medical School, Joint Center for Radiation Therapy, 50 Binney Street, 02115, Boston, Massachusetts", 
          "id": "http://www.grid.ac/institutes/grid.38142.3c", 
          "name": [
            "Harvard Medical School, Joint Center for Radiation Therapy, 50 Binney Street, 02115, Boston, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "HANNON", 
        "givenName": "EILEEN C.", 
        "id": "sg:person.0100463236.23", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0100463236.23"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Harvard Medical School, Joint Center for Radiation Therapy, 50 Binney Street, 02115, Boston, Massachusetts", 
          "id": "http://www.grid.ac/institutes/grid.38142.3c", 
          "name": [
            "Harvard Medical School, Joint Center for Radiation Therapy, 50 Binney Street, 02115, Boston, Massachusetts"
          ], 
          "type": "Organization"
        }, 
        "familyName": "HELLMAN", 
        "givenName": "SAMUEL", 
        "id": "sg:person.073733076.98", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.073733076.98"
        ], 
        "type": "Person"
      }
    ], 
    "datePublished": "1976-07", 
    "datePublishedReg": "1976-07-01", 
    "description": "HAYFLICK observed that when human foetal tissue was cultivated in vitro the cells underwent 50\u00b110 population doublings before death1. Whether this phenomenon is a property of all diploid cells in culture and is pertinent to cell renewal systems in vivo has been the subject of much discussion. Haematopoietic failure is rarely the cause of death in animal or man, presumably because this cell renewal system has a proliferative capacity which is either unlimited or, if limited, exceeds the life span of a normal animal. The proliferative capacity of the haematopoietic system, if restricted, might become exhausted when stressed by the prolonged use of cytotoxic agents. In these circumstances, significant stem cell division would be necessary to return to the steady state, thereby using much of the stem cell proliferative capacity. We have carried out experiments in mice attempting to simulate the clinical use of chemotherapeutic agents that might result in exhausting the proliferative capacity of haematopoietic stem cells. Two alkylating agents, Busulfan and L-phenylalanine (L-Pam) were investigated. Mice treated with Busulfan and to a lesser extent L-Pam demonstrate permanent damage to the proliferative capacity of surviving stem cells as measured by serial transplantation. Such data may have relevance to the use of these agents in the clinic where there is great interest in such agents to destroy presumed subclinical micrometastases in patients expected to have extended survival.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/262068a0", 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1018957", 
        "issn": [
          "0028-0836", 
          "1476-4687"
        ], 
        "name": "Nature", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "5563", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "262"
      }
    ], 
    "keywords": [
      "proliferative capacity", 
      "cause of death", 
      "stem cells", 
      "stem cell proliferative capacity", 
      "human foetal tissues", 
      "subclinical micrometastases", 
      "cell proliferative capacity", 
      "lesser extent L", 
      "haematopoietic failure", 
      "normal animals", 
      "haematopoietic stem cells", 
      "chemotherapeutic agents", 
      "cytotoxic agents", 
      "clinical use", 
      "serial transplantation", 
      "stem cell division", 
      "cell renewal systems", 
      "limited proliferation", 
      "such agents", 
      "foetal tissues", 
      "busulfan", 
      "haematopoietic system", 
      "mice", 
      "cell division", 
      "permanent damage", 
      "population doublings", 
      "renewal system", 
      "diploid cells", 
      "cells", 
      "agents", 
      "animals", 
      "life span", 
      "micrometastases", 
      "transplantation", 
      "patients", 
      "clinic", 
      "death", 
      "survival", 
      "men", 
      "cause", 
      "proliferation", 
      "vivo", 
      "extent L", 
      "tissue", 
      "subjects", 
      "use", 
      "failure", 
      "Hayflick", 
      "damage", 
      "death1", 
      "capacity", 
      "relevance", 
      "division", 
      "culture", 
      "phenylalanine", 
      "doubling", 
      "data", 
      "great interest", 
      "steady state", 
      "PAM", 
      "such data", 
      "circumstances", 
      "span", 
      "system", 
      "interest", 
      "discussion", 
      "experiments", 
      "state", 
      "phenomenon", 
      "properties", 
      "significant stem cell division"
    ], 
    "name": "Limited proliferation of stem cells surviving alkylating agents", 
    "pagination": "68-70", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1053161644"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/262068a0"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "934328"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/262068a0", 
      "https://app.dimensions.ai/details/publication/pub.1053161644"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2021-12-01T19:03", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20211201/entities/gbq_results/article/article_133.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/262068a0"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/262068a0'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/262068a0'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/262068a0'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/262068a0'


 

This table displays all metadata directly associated to this object as RDF triples.

186 TRIPLES      20 PREDICATES      107 URIs      99 LITERALS      17 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/262068a0 schema:about N3413cc07949049e79b9bd23186027adc
2 N48361b7ae8d34d2388e2b47b2abf6d95
3 N7543cfa816e04dae84135f39faf9bf8e
4 N75d5c1ac718e4775b654e7140fd9d46e
5 N824cf89426ff437ea40a69298e6e3429
6 Na1902bdd772549ba9e1f6326a56be524
7 Nb9227eea8dbe4a44980e6a5d261f9cab
8 Ncd48c5e731684c3db24cc24252b65dc6
9 Ne54c2a7334034886903941a0280e6abe
10 Ne93e7798b85d472aad2a338f4a61dd52
11 anzsrc-for:11
12 anzsrc-for:1102
13 schema:author Nf4966b641e2f4ac99d3701bee7e8f4df
14 schema:datePublished 1976-07
15 schema:datePublishedReg 1976-07-01
16 schema:description HAYFLICK observed that when human foetal tissue was cultivated in vitro the cells underwent 50±10 population doublings before death1. Whether this phenomenon is a property of all diploid cells in culture and is pertinent to cell renewal systems in vivo has been the subject of much discussion. Haematopoietic failure is rarely the cause of death in animal or man, presumably because this cell renewal system has a proliferative capacity which is either unlimited or, if limited, exceeds the life span of a normal animal. The proliferative capacity of the haematopoietic system, if restricted, might become exhausted when stressed by the prolonged use of cytotoxic agents. In these circumstances, significant stem cell division would be necessary to return to the steady state, thereby using much of the stem cell proliferative capacity. We have carried out experiments in mice attempting to simulate the clinical use of chemotherapeutic agents that might result in exhausting the proliferative capacity of haematopoietic stem cells. Two alkylating agents, Busulfan and L-phenylalanine (L-Pam) were investigated. Mice treated with Busulfan and to a lesser extent L-Pam demonstrate permanent damage to the proliferative capacity of surviving stem cells as measured by serial transplantation. Such data may have relevance to the use of these agents in the clinic where there is great interest in such agents to destroy presumed subclinical micrometastases in patients expected to have extended survival.
17 schema:genre article
18 schema:isAccessibleForFree false
19 schema:isPartOf Ndb2f033274004b838b948e64d1c15cc2
20 Nfd481a1c6cf4413ab4c0feaff5f7f3c2
21 sg:journal.1018957
22 schema:keywords Hayflick
23 PAM
24 agents
25 animals
26 busulfan
27 capacity
28 cause
29 cause of death
30 cell division
31 cell proliferative capacity
32 cell renewal systems
33 cells
34 chemotherapeutic agents
35 circumstances
36 clinic
37 clinical use
38 culture
39 cytotoxic agents
40 damage
41 data
42 death
43 death1
44 diploid cells
45 discussion
46 division
47 doubling
48 experiments
49 extent L
50 failure
51 foetal tissues
52 great interest
53 haematopoietic failure
54 haematopoietic stem cells
55 haematopoietic system
56 human foetal tissues
57 interest
58 lesser extent L
59 life span
60 limited proliferation
61 men
62 mice
63 micrometastases
64 normal animals
65 patients
66 permanent damage
67 phenomenon
68 phenylalanine
69 population doublings
70 proliferation
71 proliferative capacity
72 properties
73 relevance
74 renewal system
75 serial transplantation
76 significant stem cell division
77 span
78 state
79 steady state
80 stem cell division
81 stem cell proliferative capacity
82 stem cells
83 subclinical micrometastases
84 subjects
85 such agents
86 such data
87 survival
88 system
89 tissue
90 transplantation
91 use
92 vivo
93 schema:name Limited proliferation of stem cells surviving alkylating agents
94 schema:pagination 68-70
95 schema:productId N053201121e3544689ec2d1c3b9b8be94
96 N8953e1a74e684924b07b4b97ebe285bb
97 Na8a2a7d8852d4e738530a69268833749
98 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053161644
99 https://doi.org/10.1038/262068a0
100 schema:sdDatePublished 2021-12-01T19:03
101 schema:sdLicense https://scigraph.springernature.com/explorer/license/
102 schema:sdPublisher N0f216532d0624719a95e884e0dbe0888
103 schema:url https://doi.org/10.1038/262068a0
104 sgo:license sg:explorer/license/
105 sgo:sdDataset articles
106 rdf:type schema:ScholarlyArticle
107 N053201121e3544689ec2d1c3b9b8be94 schema:name dimensions_id
108 schema:value pub.1053161644
109 rdf:type schema:PropertyValue
110 N0f216532d0624719a95e884e0dbe0888 schema:name Springer Nature - SN SciGraph project
111 rdf:type schema:Organization
112 N2e8c890f9ea64c64858d291b6bcbefe7 rdf:first sg:person.073733076.98
113 rdf:rest rdf:nil
114 N3413cc07949049e79b9bd23186027adc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
115 schema:name Mice, Inbred C3H
116 rdf:type schema:DefinedTerm
117 N48361b7ae8d34d2388e2b47b2abf6d95 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
118 schema:name Mice
119 rdf:type schema:DefinedTerm
120 N7543cfa816e04dae84135f39faf9bf8e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
121 schema:name Phenylalanine
122 rdf:type schema:DefinedTerm
123 N75d5c1ac718e4775b654e7140fd9d46e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
124 schema:name Bone Marrow Cells
125 rdf:type schema:DefinedTerm
126 N824cf89426ff437ea40a69298e6e3429 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
127 schema:name Busulfan
128 rdf:type schema:DefinedTerm
129 N8953e1a74e684924b07b4b97ebe285bb schema:name doi
130 schema:value 10.1038/262068a0
131 rdf:type schema:PropertyValue
132 Na1902bdd772549ba9e1f6326a56be524 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
133 schema:name Cell Division
134 rdf:type schema:DefinedTerm
135 Na8a2a7d8852d4e738530a69268833749 schema:name pubmed_id
136 schema:value 934328
137 rdf:type schema:PropertyValue
138 Nb26ade9b4e674264ba1d7da9b3796f34 rdf:first sg:person.0100463236.23
139 rdf:rest N2e8c890f9ea64c64858d291b6bcbefe7
140 Nb9227eea8dbe4a44980e6a5d261f9cab schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
141 schema:name Animals
142 rdf:type schema:DefinedTerm
143 Ncd48c5e731684c3db24cc24252b65dc6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name Bone Marrow
145 rdf:type schema:DefinedTerm
146 Ndb2f033274004b838b948e64d1c15cc2 schema:volumeNumber 262
147 rdf:type schema:PublicationVolume
148 Ne54c2a7334034886903941a0280e6abe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
149 schema:name Male
150 rdf:type schema:DefinedTerm
151 Ne93e7798b85d472aad2a338f4a61dd52 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
152 schema:name Hematopoietic Stem Cells
153 rdf:type schema:DefinedTerm
154 Nf4966b641e2f4ac99d3701bee7e8f4df rdf:first sg:person.074622136.37
155 rdf:rest Nb26ade9b4e674264ba1d7da9b3796f34
156 Nfd481a1c6cf4413ab4c0feaff5f7f3c2 schema:issueNumber 5563
157 rdf:type schema:PublicationIssue
158 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
159 schema:name Medical and Health Sciences
160 rdf:type schema:DefinedTerm
161 anzsrc-for:1102 schema:inDefinedTermSet anzsrc-for:
162 schema:name Cardiorespiratory Medicine and Haematology
163 rdf:type schema:DefinedTerm
164 sg:journal.1018957 schema:issn 0028-0836
165 1476-4687
166 schema:name Nature
167 schema:publisher Springer Nature
168 rdf:type schema:Periodical
169 sg:person.0100463236.23 schema:affiliation grid-institutes:grid.38142.3c
170 schema:familyName HANNON
171 schema:givenName EILEEN C.
172 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0100463236.23
173 rdf:type schema:Person
174 sg:person.073733076.98 schema:affiliation grid-institutes:grid.38142.3c
175 schema:familyName HELLMAN
176 schema:givenName SAMUEL
177 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.073733076.98
178 rdf:type schema:Person
179 sg:person.074622136.37 schema:affiliation grid-institutes:grid.38142.3c
180 schema:familyName BOTNICK
181 schema:givenName LESLIE E.
182 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.074622136.37
183 rdf:type schema:Person
184 grid-institutes:grid.38142.3c schema:alternateName Harvard Medical School, Joint Center for Radiation Therapy, 50 Binney Street, 02115, Boston, Massachusetts
185 schema:name Harvard Medical School, Joint Center for Radiation Therapy, 50 Binney Street, 02115, Boston, Massachusetts
186 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...