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Studies of the mechanism of action of urethane in initiating pulmonary adenomas in mice. II. Its relation to nucleic acid synthesis.
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MedLine Citation:
PMID:  13416469     Owner:  NLM     Status:  OLDMEDLINE    
The process of carcinogenesis following exposure of mice to urethane is demonstrated in the present work to be intimately related to nucleic acid synthesis. Injection of animals with a DNA hydrolysate immediately prior to a single exposure of the animals to urethane markedly reduced the number of pulmonary adenomas initiated. Aminopterin, known to interfere in nucleic acid synthesis (46), potentiated the carcinogenic action of urethane and this potentiation was blocked by injection of a DNA hydrolysate. Of the components and precursors of nucleic acids the pyrimidine series seemed especially concerned. Alterations in the utilization of oxaloacetate, ureidosuccinic acid, dihydro-orotic acid, orotic acid, cytidylic acid, and thymine appeared to be critical steps in the oncogenic process, following upon the primary disorder of cellular metabolism initiated by the carcinogen. All these substances except oxaloacetate profoundly reduced the number of tumors initiated by urethane. Oxaloacetate potentiated the carcinogenic effect. When these results are viewed together and in relation to known facts concerning nucleic acid synthesis they provide evidence suggesting that the point of action of the carcinogen is in the pathway of nucleic acid synthesis below orotic acid and perhaps at the level of ureidosuccinic acid. The potentiating influence of adenine, 4-amino-5-imidazole carboxamide, and aminopterin, the lack of effect of uracil, and the inhibitory influence of thymine together suggest that DNA rather than RNA is the nucleic acid critical to the oncogenic response of mice to urethane.
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of experimental medicine     Volume:  105     ISSN:  0022-1007     ISO Abbreviation:  J. Exp. Med.     Publication Date:  1957 Apr 
Date Detail:
Created Date:  1957-12-01     Completed Date:  2002-05-01     Revised Date:  2010-09-21    
Medline Journal Info:
Nlm Unique ID:  2985109R     Medline TA:  J Exp Med     Country:  Not Available    
Other Details:
Languages:  eng     Pagination:  279-306     Citation Subset:  OM    
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MeSH Terms
Neoplasms / metabolism*
Nucleic Acids / metabolism*
Reg. No./Substance:
0/Nucleic Acids

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): J Exp Med
ISSN: 0022-1007
ISSN: 1540-9538
Publisher: The Rockefeller University Press
Article Information
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Copyright © Copyright, 1957, by The Rockefeller Institute for Medical Research New York
Received Day: 19 Month: 12 Year: 1956
Print publication date: Day: 31 Month: 3 Year: 1957
Volume: 105 Issue: 4
First Page: 279 Last Page: 306
ID: 2136699
PubMed Id: 13416469

Stanfield Rogers
From the Department of Pathology, Duke University School of Medicine, Durham

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