Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by de Kok, A.J.
Right arrow Articles by Engelse, L.D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Kok, A.J.
Right arrow Articles by Engelse, L.D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1985 Oxford University Press

research-article

Genetic and molecular mechanisms of the in vitro transformation of Syrian hamster embryo cells by the carcinogen N-ethyl-N-nitrosourea II. Correlation of morphological transformation, enhanced fibrinolytic activity, gene mutations, chromosomal alterations and lethality to specific carcinogen-induced DNA lesions

A.J. de Kok , A.A. van Zeeland , J.W.I.M. Simons  and L.Den Engelse 1

Department of Radiation Genetics and Chemical Mutagenesis, Sylvius Laboratories, State University of Leiden Wassenaarseweg 72, 2333 AL, Leiden
1Division of Chemical Carcinogenesis, The Netherlands Cancer Institute, (Antoni van Leeuwenhoek Huis) Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

The stability of N-ethyl-N-nitrosourea (ENU)-induced DNA damage in Syrian hamster embryo (SHE) cells was determined to study correlations with ENU-induced mutation and transformation. Confluent cultures were treated with ENU and after 0, 3 or 6 days holding in low serum medium to inhibit cell proliferation, the extent of ethylation at different sites in the DNA was determined with h.p.l.c. The amounts of dTp(Et)dT-triester, and O4- and O2-EtThy remained constant during the 6-day period. O6-EtGua slowly decreased (t1/2: 14 days); the initial level was lower than expected from in vitro data, suggesting that Syrian hamster embryo cells contain alkyl transferase. Evidence for active removal was also obtained in the case of 7-EtGua (t1/2: 59 h), O2-EtCyt (t1/2: 96 h) and possibly 3-EtGua (t1/2: 102 h). As expected, the pro-mutagenic O6-EtGua was found to correlate with gene mutations. In addition, however, we have found that the likewise promutagenic O4- and O2-EtThy also correlate with gene mutations. Furthermore, our data suggest that sister chromatid exchange (SCE) and cytotoxicity (clonal survival) have a similar molecular basis. Both correlate with O2-EtCyt and 3-EtGua which are located in the narrow groove and are therefore expected to block DNA replication. Chromatid aberrations and micronuclei could not be correlated to specific DNA lesions, but were found to correlate mainly to N-ethy-lations. The same holds for morphological transformation, but in this case there is also a small contribution of DNA O-ethylation. In contrast, enhanced fibrinolytic activity did correlate only with stable O-ethylations, including O6-EtGua.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.