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International Journal of Toxicology
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Articles

In Vitro Testing of Cyto- and Genotoxicity of New Porphyrin Water-Soluble Metal Derivatives

Gennadi Gasparyan

Department of Genetics and Cytology, Yerevan State University, Yerevan, Armenia; and Institute of Zoology of Armenian NAS, Yerevan, Armenia

Galina Hovhannisyan

Department of Genetics and Cytology, Yerevan State University, Yerevan, Armenia

Robert Ghazaryan
Lida Sahakyan
Artak Tovmasyan

Department of General and Organic Chemistry, Yerevan State Medical University, Yerevan, Armenia

Rusanna Grigoryan
Natalia Sarkissyan

Laboratory of Genetics, Institute of Zoology of Armenian NAS, Yerevan, Armenia

Samvel Haroutiunian
Rouben Aroutiounian

Department of Genetics and Cytology, Yerevan State University, Yerevan, Armenia

Correspondence: Address correspondence to Dr. Gennadi Gasparyan, Department of Genetics and Cytology, Biological Faculty, Yerevan State University, 1 Manoogian Str., Yerevan 0025. E-mail:gena{at}ysu.am

Porphyrins and porphyrin derivatives have an outstanding potential for discovery of novel pharmacological agents due to their ability for numerous chemical modifications and a variety of mechanisms of biological effects. New water-soluble Ag and Zn derivatives of tetrachloride meso-tetra (4-N-oxiethylpyridyl) porphyne were synthesized. Cyto- and genotoxicity of these substances were tested in vitro by the vital dye (trypan blue) exclusion and the micronucleus tests, respectively. Both metalloporphyrins were shown to be cytotoxic for Cos-7 (fibroblast-like African green monkey kidney cells transformed by simian virus 40 [SV40]), DU 145 (epithelial-like cells of human prostate carcinoma), and K-562 (human chronic myeloid leukemia cells) cell lines. At the same time they did not cause chromosome fragmentation in K-562 cell line at as high concentrations as IC50 (20 µmol/L for Ag and 70 µmol/L for Zn derivative). Thus, the metalloporphyrins tested meet at least two important demands to potential anticancer drugs as they combine the cytotoxicity with low genotoxicity. The three in vitro tumor models used are relevant to further in vitro and in vivo pre-clinical investigation of the studied metalloporphyrins as potential chemotherapeutics.

Key Words: Cytotoxicity • Genotoxicity • In Vitro Testing • Porphyrin Metal Derivatives

International Journal of Toxicology, Vol. 26, No. 6, 497-502 (2007)
DOI: 10.1080/10915810701707056
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