GENOTOXICITY OF THE SYSTEMIC ANTIFUNGAL ANTIBIOTIC AMPHOTERICIN-B IN-VITRO

The mutagenic potentials of the systemic antifungal antibiotic, Amphotericin B, listed as an essential drug by W.H.O., were evaluated using the human lymphocyte in vitro test system by assaying conventional chromosome aberrations and sister chromatid exchanges (SCEs) from recommended protocols. Cultures were initiated from blood of normal human volunteers, not exposed to any drugs or other agents. The drug was added at various time points to the cultures at therapeutic blood volume level concentrations. Strict controls of sterile doubly distilled water and sodium deoxycholate used with the drug, as a vehicle for administration, were employed under conditions identical to their experimental counterparts. Inhibition of cell proliferation by the controlled was estimated by scoring 1st, 2nd and 3rd metaphases from cultures used for SCE analysis. The drug induced chromosome aberrations and SCEs to a significant extent. Sodium deoxycholate did not cause chromosome aberrations but significantly induced SCEs. Induction of SCEs was higher in drug-exposed samples. These suggest the existence of synergism between sodium deoxycholate and Amphotericin B. Both inhibited cell division which is evident from the distribution pattern of M(1), M(2) and M(3) metaphases. These results indicate the genotoxic potential of the drug in vitro.