Increased cytotoxicity of 1-(2-chloroethyl)-1-nitroso-3(4-methyl)-cyclohexylurea by pretreatment with O6-methylguanine in resistant but not in sensitive human melanoma cells.

Abstract

Cells from a resistant ("Gr II") and a sensitive ("Str") human melanoma xenograft were incubated in vitro with O6-methylguanine for 2 h, subsequently treated with 1-(2-chloroethyl)-1-nitroso-3(4-methyl)-cyclohexylurea (MeCCNU) for 1 h and then plated in soft agar. In the resistant cells the O6-methylguanine pretreatment (2 mM) yielded an increase in sensitivity towards MeCCNU by a factor of 7.5. In the sensitive melanoma cells pretreatment with O6-methylguanine did not increase cytotoxicity. Human bone marrow cells from three normal donors were similarly pretreated with O6-methylguanine and MeCCNU. There was a clear increase in MeCCNU-induced cytotoxicity. We conclude, that while O6-methylguanine does potentiate the action of MeCCNU in resistant melanoma cells, the therapeutic usefulness of this treatment strategy may be limited.

• Authors: W Dempke, P Nehls, U Wandl, D Soll, C G Schmidt, R Osieka
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 113 Issue 4 Pg. 387-91 ( 1987) ISSN: 0171-5216 [Print] Germany
• PMID: 3597524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cross-Linking Reagents
• Nitrosourea Compounds
• Semustine
• Guanine
• O-(6)-methylguanine

Topics

• Animals
• Bone Marrow (drug effects)
• Bone Marrow Cells
• Cell Division (drug effects)
• Colony-Forming Units Assay
• Cross-Linking Reagents
• Drug Resistance
• Drug Synergism
• Guanine (analogs & derivatives, pharmacology)
• Humans
• Melanoma (pathology)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Nitrosourea Compounds (pharmacology)
• Semustine (pharmacology)
• Transplantation, Heterologous
• Tumor Stem Cell Assay