Cytogenetic effects of 8-Cl-cAMP on human and animal chromosomes

Abstract

Purpose: To assess the cytogenetic effects in vitro and in vivo of a non-cytotoxic antitumor agent with biomodulator activity, 8-chloro-3′,5′ cyclic adenosine monophosphate (8-Cl-cAMP). Materials and methods: Cytogenetic effects of 8-Cl-cAMP where evaluated using the in vitro chromosome cytogenetic assay (CA) on human peripheral blood lymphocytes of healthy individuals and by bone marrow micronucleus assay in adult BALB/c mice. Results: In the in vitro chromosome CA, 8-Cl-cAMP (in all respective doses; 1.5 and 15 μm) induced mitotic inhibition and premature centromere separation (PCS) but no chromosomal damage in cultured human peripheral blood lymphocytes. In the in vivo test, single intraperitoneal (i.p.) injection of 8-Cl-cAMP in doses of 10,80 and 150 mg/kg showed a dose-related effect on the frequency of micronuclei, detected in murine polychromatic erythrocytes (PCE). Conclusion: The results of the present study show that genotoxicity of 8-Cl-cAMP has a different matrix of response when comparing results in vitro and in vivo, suggesting that high metabolic activity in vivo is responsible for the clastogenic potential of 8-Cl-cAMP. These comparative results indicate a need of having an available battery of genotoxic tests in order to evaluate possible cytogenetic effects of novel antitumor agents.