ArticleProceedings of the National Academy of Sciences of the United States of America1995
Heritable, population-wide damage to cells as the driving force of neoplastic transformation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 34 citations in OpenAlex.
- Forward and reverse mutations in stages of cancer development.Human genomics · 2018Article
- Degrees and kinds of selection in spontaneous neoplastic transformation: an operational analysis.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis.Oncogene · 2002Review
- Coculturing diverse clonal populations prevents the early-stage neoplastic progression that occurs in the separate clones.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Relation of the slow growth phenotype to neoplastic transformation: possible significance for human cancer.In vitro cellular & developmental biology. Animal · 1999Article
- Clonal dynamics of progressive neoplastic transformation.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
- The cellular ecology of progressive neoplastic transformation: a clonal analysis.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
- Ubiquitous, heritable damage in cell populations that survive treatment with methotrexate.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Irreversibility of cellular aging and neoplastic transformation: a clonal analysis.Proceedings of the National Academy of Sciences of the United States of America · 1996Article
- Cellular aging, destabilization, and cancer.Proceedings of the National Academy of Sciences of the United States of America · 1996Article
- Neoplastic development: paradoxical relation between impaired cell growth at low population density and excessive growth at high density.Proceedings of the National Academy of Sciences of the United States of America · 1995Article
- Unmasking large and persistent reductions in proliferation rate of aging cells.In vitro cellular & developmental biology. AnimalArticle
- Quantitative aspects of the selective killing of transformed cells by methotrexate in the presence of leucovorin.In vitro cellular & developmental biology. AnimalArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prolonged incubation of NIH 3T3 cells under the growth constraint of confluence results in the death of some cells in a manner suggestive of apoptosis. Successive rounds of prolonged incubation at confluence of the surviving cells produce increasing neoplastic transformation in the form of increments in saturation density and transformed focus formation. Cells from the postconfluent cultures are given a recovery period of various lengths to remove the direct inhibitory effect of confluence before their growth properties are studied. It is found that with each round of confluence the exponential growth rate of the cells at low densities gets lower and the size of isolated colonies of the same cells shows a similar progressive reduction. The decreased growth rate of cells from the third round of confluence persists for > 60 generations of growth at low density. The proportion of colonies containing giant cells is much higher after a 2-day recovery from confluence than after a 7-day recovery. Retardation of growth at low density and increased saturation density appear to be two sides of the same coin: both occur in the entire population of cells and precede the formation of transformed foci. We propose that the slowdown in growth and the formation of giant cells result from heritable damage to the cells, which in turn drives their transformation. Similar results have been reported for the survivors of x-irradiation and of treatment with chemical carcinogens and are associated with the aging process in animals. We suggest that these changes result from free radical damage to membrane lipids with particular damage to lysosomes. Proteases and nucleases would then be released to progressively modify the growth behavior and genetic stability of the cells toward autonomous proliferation.
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