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PMID: 2308938 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

DNA amplification is rare in normal human cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 5 ·1990-03-00 ·Pages 1791-5

Wright JA, Smith HS, Watt FM, Hancock MC, Hudson DL, Stark GR

Abstract

Three types of normal human cells were selected in tissue culture with three drugs without observing a single amplification event from a total of 5 x 10(8) cells. No drug-resistant colonies were observed when normal foreskin keratinocytes were selected with N-(phosphonacetyl)-L-aspartate or with hydroxyurea or when normal mammary epithelial cells were selected with methotrexate. Some slightly resistant colonies with limited potential for growth were obtained when normal diploid fibroblast cells derived from fetal lung were selected with methotrexate or hydroxyurea but careful copy-number analysis of the dihydrofolate reductase and ribonucleotide reductase genes revealed no evidence of amplification. The rarity of DNA amplification in normal human cells contrasts strongly with the situation in tumors and in established cell lines, where amplification of oncogenes and of genes mediating drug resistance is frequent. The results suggest that tumors and cell lines have acquired the abnormal ability to amplify DNA with high frequency.

MeSH Terms
Breast Cells, Cultured DNA/genetics Diploidy Drug Resistance Epithelial Cells Epithelium/drug effects,metabolism Female Fibroblasts/cytology,drug effects Gene Amplification Humans Hydroxyurea/pharmacology Immunoblotting Infant, Newborn Keratinocytes/cytology,metabolism Male Methotrexate/pharmacology
Chemicals
DNA Hydroxyurea Methotrexate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wright J A
Imperial Cancer Research Fund Laboratories, London, United Kingdom.
Smith H S
Watt F M
Hancock M C
Hudson D L
Stark G R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.5.1791
Published
1990-03-00
Pages
1791-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC53569
Subset
IM
Grants
NCI NIH HHS · T01CA44768 · United States
External Links
PubMed source DOI: 10.1073/pnas.87.5.1791 PMC Full Text View journal details
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