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Genotoxicity of Some Metal-Based Antineoplastics, Evaluated by SOS Chromotest and Cytogenetic Analysis

C Socaciu1, L Pasca, C Silvestru

  • 1Department of Biochemistry University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca RO-3400 Romania.

Metal-Based Drugs
|January 1, 1996
PubMed

Insights

This study screened metal-based antineoplastic drugs Romcis and diphenylantimony(III) diisopropyldithiophosphate (PADTF) for mutagenicity. Both drugs showed mutagenic potential, similar to cyclophosphamide, indicating risks associated with these cancer treatments.

Area of Science:

  • Pharmacology
  • Toxicology
  • Genetics

Background:

  • Metal-based antineoplastic drugs are crucial in cancer therapy.
  • Assessing the mutagenic potential of these drugs is vital for patient safety.
  • Cyclophosphamide serves as a benchmark for mutagenicity testing.

Purpose of the Study:

  • To evaluate the mutagenic potential of Romcis and diphenylantimony(III) diisopropyldithiophosphate (PADTF).
  • To compare the mutagenicity of these metal-based drugs with cyclophosphamide.
  • To investigate the effects of metabolic activation on drug-induced mutagenicity.

Main Methods:

  • Utilized the SOS Chromotest in E. coli PQ 37 cultures with varying compound doses.
  • Performed cytogenetic analysis on leukocyte cultures.
  • Conducted tests with and without metabolic activation (S(9)-mix).

Main Results:

  • Cyclophosphamide exhibited indirect mutagenic potential, enhanced by S(9)-mix, and showed antiproliferative/clastogenic effects on lymphocytes.
  • Romcis and PADTF demonstrated significant positive responses in the SOS Chromotest.
  • Increased frequencies of chromosomal aberrations correlated with SOS Chromotest results for Romcis and PADTF.

Conclusions:

  • Romcis and PADTF possess mutagenic potential, confirmed by both bacterial and mammalian cell assays.
  • The findings highlight the need for careful risk-benefit assessment of these metal-based antineoplastic agents.
  • Further research into the genotoxic mechanisms of Romcis and PADTF is warranted.

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