engleski

GENOTOXIC DETERMINATION OF TWO NOVEL MONOMETHINE CYANINE DERIVATIVES

Pharmacology testing of new compound implies determination of toxicity and genotoxicity following potential antimicrobial, antitumor or some other healing effects [1]. Genotoxicity induced by a chemical is based on ability of compound to cause mutation or change in genome. In development of possible new healing compound as a part of safety assessment procedure it is necessary to conduct mutagenicity testing. Mutation test systems are divided in long-term and short-term systems [2]. One of the mostly applied and reliable short-term system for genotoxicity testing is AMES or, the so-called Salmonella/ microsome test [3]. A compound is considered mutagenic when the increase in dose is directly related to the increase in number of colonies mutated in one or more strains of Salmonella typhimurium dependent histidine [4]. In this work two novel monomethine cyanine derivatives (MCD 4, 8) in concentration range from 10-4 M to 10-6 M were tested for genotoxic effect on two Salmonella modified strains designated as TA100 and TA1535 and one E.colli WP2 strain/tryptophan addicted. Test was conducted according to MOLTOX protocol without S9 enzyme activation system. All experiments were performed in duplicate and results expressed as mutagenicity index (MI). Results show no difference in number of revertants colonies among negative controls and MCD 4 and 8 for WP2 and TA1535 (MI=0-1). Strain TA100 indicate for MCD 4 at the 10-6 M concentration MI=1, 9, while other tested concentrations resulted with MI=0. MCD 8 at concentrations 10-4 M and 10-6 M resulted with MI = 0-1. Results indicate that tested MCD 8 is not mutagenic while MCD 4 depending on applied concentration (10-6 M) can be considered as weak mutagen. Additional testing is mandatory for final decision on mutagenic ability of MCD 4.

genotoxicity; mutagen; Ames test

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