Potential antitumour mitosenes: relationship between in vitro DNA interstrand cross-link formation and DNA damage in escherichia coli K-12 strains

Share/Save/Bookmark

Maliepaard, Marc and Sitters, Karin A.M.C. and Mol, Nico J. de and Janssen, Lambert H.M. and Stratford, Ian J. and Stephens, Miriam and Verboom, Willem and Reinhoudt, David N. (1994) Potential antitumour mitosenes: relationship between in vitro DNA interstrand cross-link formation and DNA damage in escherichia coli K-12 strains. Biochemical Pharmacology, 48 (7). pp. 9320-9323. ISSN 0006-2952

open access
[img]
Preview
PDF
585kB
Abstract:This investigation was aimed at determining the possible relationship between DNA interstrand cross-linking and the cytotoxic activity of potential antitumour mitosene compounds. Mitosenes, possessing two good leaving groups at C-1 and C-10, were found to be able to cross-link calf thymus DNA under hypoxic conditions following sodium dithionite (Na2S2O4) reduction at pH 7.0 and pH 5.5. DNA interstrand cross-linking was pH dependent for most of the mitosenes used, with a higher amount of cross-links formed at pH 5.5 compared to pH 7.0. Without reduction or under aerobic conditions no cross-link formation was detected. The importance of DNA damage for the toxic effect of these mitosenes was assayed by comparing the survival in a DNA repair deficient and a DNA repair proficient E. coli K-12 strain. A correlation between the number of cross-links formed in calf thymus DNA in vitro and the 50 values in the DNA repair deficient E. coli strain was found. The effect of hypoxia on toxicity of mitosenes was studied in Chinese hamster V79 cells. In these cells, mitosenes appeared to be very active. Under severe hypoxic conditions toxicity of these mitosenes increased, most likely due to the increased lifetime of the activated mitosene species as compared to aerobic conditions. The results suggest that DNA cross-linking following reductive activation is important for the eventual activity of mitosenes in a bacterial system. Increased activity of mitosenes under hypoxic conditions in the V79 cells indicates that these mitosenes may be more active in hypoxic parts of tumours.
Item Type:Article
Copyright:© 1994 Elsevier Science
Faculty:
Science and Technology (TNW)
Research Group:
Link to this item:http://purl.utwente.nl/publications/12346
Official URL:http://dx.doi.org/10.1016/0006-2952(94)90559-2
Export this item as:BibTeX
EndNote
HTML Citation
Reference Manager

 

Repository Staff Only: item control page

Metis ID: 106617