Chemical Carcinogen-Induced Decreases in Genomic 5-methyldeoxycytidine Content of Normal Human Bronchial Epithelial Cells

The genomic content of DNA 5-methyldeoxycytidine (m5dC) was measured in dividing normal human bronchial epithelial cells treated with a broad range of chemical carcinogens. At noncytotoxic concentrations, all of the carcinogenic agents tested significantly reduced cellular DNA m5dC content whereas t...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1987-05, Vol.84 (10), p.3298-3301
Main Authors: Wilson, Vincent L., Smith, Ruth A., Longoria, Jim, Liotta, Mary Anne, Harper, Cynthia M., Harris, Curtis C.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Carcinogenesis
Carcinogens
Carcinogens - pharmacology
Cell lines
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cells
Cells, Cultured
Cultured cells
Deoxycytidine - analogs & derivatives
Deoxycytidine - metabolism
DNA
DNA - drug effects
Epithelial Cells
Fundamental and applied biological sciences. Psychology
Genes
Genomics
Humans
Lung - cytology
Lung - drug effects
Molecular and cellular biology
Phenanthrenes
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Summary:The genomic content of DNA 5-methyldeoxycytidine (m5dC) was measured in dividing normal human bronchial epithelial cells treated with a broad range of chemical carcinogens. At noncytotoxic concentrations, all of the carcinogenic agents tested significantly reduced cellular DNA m5dC content whereas the weakly carcinogenic and noncarcinogenic agents, benzo[e]pyrene and phenanthrene (respectively), did not. These reductions varied from 8% to 31% depending on the agent and the donor cells. The reductions in genomic m5dC levels were concentration dependent for the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene. We speculate that carcinogen-induced perturbation of DNA m5dC patterns may lead to heritable changes in gene expression and contribute to the molecular alterations involved in the initiation and the subsequent steps of the carcinogenesis process.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.84.10.3298