The alkylating antitumor drug tallimustine does not induce DNA repair

Tallimustine, an alkylating benzoyl mustard derivative of distamycin A (FCE 24517), is a novel anti-tumor agent. Both its cytotoxic activity against human LoVo cells and nicking efficiency on isolated plasmid DNA were studied in relation to hyperthermic treatment and compared to the effect of doxoru...

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Bibliographic Details
Published inAnticancer research Vol. 16; no. 6B; p. 3779
Main Authors Rossi, R, Montecucco, A, Capolongo, L, Mezzina, M, Chevallier-Lagente, O, Sarasin, A, Ciarrocchi, G
Format Journal Article
LanguageEnglish
Published Greece 01.11.1996
Subjects
Antibiotics, Antineoplastic - pharmacology
Antineoplastic Agents, Alkylating - pharmacology
Distamycins - pharmacology
DNA Damage - drug effects
DNA Damage - genetics
DNA Repair - drug effects
DNA Repair - genetics
DNA, Neoplasm - drug effects
DNA, Neoplasm - radiation effects
DNA, Superhelical - drug effects
DNA, Superhelical - radiation effects
Doxorubicin - pharmacology
Genes, Reporter - genetics
Humans
Hyperthermia, Induced
Luciferases - genetics
Luciferases - metabolism
Nitrogen Mustard Compounds - pharmacology
Transfection
Tumor Cells, Cultured - drug effects
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Summary:Tallimustine, an alkylating benzoyl mustard derivative of distamycin A (FCE 24517), is a novel anti-tumor agent. Both its cytotoxic activity against human LoVo cells and nicking efficiency on isolated plasmid DNA were studied in relation to hyperthermic treatment and compared to the effect of doxorubicin, a known non-alkylating anti-tumor agent. The results of this analysis indicate that the cytotoxic activity of tallimustine reflects its direct interaction with the DNA target. The ability of tallimustine to induce DNA repair in human primary normal fibroblasts was monitored by determining both the stimulation of unscheduled DNA synthesis (UDS) and the ability to reactivate a plasmid containing a reporter gene, treated in vitro with tallimustine, in comparison with the effect of UV-C irradiation. The results suggest that human cells able to repair UV-damage arc unable to overcome DNA damage induced by tallimustine. Therefore, the hypothesis that the biological activity of tallimustine is related to its alkylating properties is further supported by the temperature studies and strengthened by the observed inability of cells to repair tallimustine-induced DNA damage.
ISSN:0250-7005