Publication

Different type of DNA damage caused by three aziridinyl substituted cyclophosphazenes in a human small cell lung carcinoma cell line

Zijlstra, J. G., de Jong, S., van de Grampel, J. C., de Vries, L. & Mulder, N. H., Jun-1986, In : Cancer Research. 46, 6, p. 2726-2729 4 p.

Research output: Contribution to journalArticleAcademicpeer-review

Aziridinyl substituted cyclophosphazenes are a new group of inorganic chemical agents with in vitro and in vivo cytotoxic activity. We investigated the mode of action on DNA of three different compounds, 1,3,3,5,5-pentakis (1-aziridinyl)-1 lambda 6,2,4,6,3 lambda 5,5 lambda 5-thiatriazadiphosphorine -1-oxide (SOAz), trans-1,3-bis(1-aziridinyl)-1,3,5,5-tetrakis (methylamino)-2,4,6,1 lambda 5,3 lambda 5,5 lambda 5-triazatriphosphorine (AZP), and 1,trans-5-bis(1-azaridinyl)-gem-1,3,3'-cis-5,7,7'-hexakis (methylamino)-2,4,6,8,1 lambda 5,3 lambda 5,5 lambda 5,7 lambda 5 -tetraazatetraphosophocine (AZM), of this group in the Ehrlich ascites tumor cell line (EAT) and a human small cell carcinoma cell line. The DNA damage was evaluated by alkaline elution and ethidium bromide fluorescence assay. Each compound gave a different pattern of DNA damage. SOAz caused neither single strand breaks nor cross-links, AZP gave cross-links, and AZM gave single strand breaks and cross-links in both cell lines after drug incubation for 6 h. The range of concentrations leading to cytoxicity of AZP and AZM in the clonogenic assay coincided with the concentrations leading to DNA damage. Cell kill occurred with SOAz in the same range of concentrations, however, without detectable evidence of DNA damage. It was concluded that cyclophosphazenes are probably a heterogeneous group as far as their mode of action as cytostatic agents is concerned.

Original languageEnglish
Pages (from-to)2726-2729
Number of pages4
JournalCancer Research
Volume46
Issue number6
Publication statusPublished - Jun-1986

    Keywords

  • Animals, Antineoplastic Agents, Aziridines, Azirines, Carcinoma, Ehrlich Tumor, Carcinoma, Small Cell, Cell Line, Cross-Linking Reagents, DNA, Neoplasm, Ethidium, Humans, Lung Neoplasms, Mice

ID: 6175967