Cytogenetic effects of 1-p-(3-methyltriazeno)benzoic acid potassium salt on human lymphocytes in vitro.
The triazene derivative 1-p-(3-methyltriazeno)benzoic acid potassium salt (MTBA) shows pharmacological properties similar to those of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC, trade name dacarbazine), which is known to induce antigenic modulation in tumor cells (xenogenization) and is currently used in cancer therapy. Mutagenic, teratogenic and cancerogenic properties of triazene derivatives have been demonstrated but there is no report on their possible clastogenicity. We describe here the in vitro cytogenetic effects of MTBA on human peripheral blood lymphocytes. The drug was tested at different culture times in a range of concentrations from 2 to 500 micrograms/ml. MTBA caused a dose-dependent increase in the frequency of chromosomal breaks. Different blood donors showed different sensitivity to the treatment. Cell proliferation, as evaluated by [3H]thymidine incorporation, was inhibited at the highest concentrations of the drug. These data might be relevant for comparison with in vivo effects of the drug in clinical trials and to investigate the possible relations between xenogenization induced by MTBA and its genetic and cytogenetic effects in human lymphocytes.
Vernole
P
P
Department of Public Health, 2nd University of Rome, Italy.
Caporossi
D
D
Tedeschi
B
B
Porfirio
B
B
Melino
G
G
Bonmassar
E
E
Nicoletti
B
B
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D014226:Triazenes / Q000494:pharmacology*
D014226:Triazenes; C053777:1-4-(3-methyltriazeno)benzoic acid