DNA amplification is rare in normal human cells

Journal Article · Thu Mar 01 00:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.5.1791· OSTI ID:6152961

Wright, J A; Watt, F M; Hudson, D L; Stark, G R ^[1]; Smith, H S; Hancock, M C ^[2]

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1. Imperial Cancer Research Fund Labs., London (England)
2. Peralta Cancer Research Institute, Oakland, CA (USA)

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{sup 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 onogenes 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.

• OSTI ID: 6152961
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:5; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
FIBROBLASTS
GENE AMPLIFICATION
HYDROXYUREA
BIOLOGICAL EFFECTS
METHOTREXATE
CELL CULTURES
EPIDERMIS
KERATIN
MAMMARY GLANDS
MAN
NEOPLASMS
TUMOR CELLS
AMIDES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIMETABOLITES
BODY
CONNECTIVE TISSUE CELLS
DISEASES
DRUGS
EPITHELIUM
GLANDS
HYDROXY COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PRIMATES
PROTEINS
SCLEROPROTEINS
SKIN
SOMATIC CELLS
TISSUES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques