Antimutagenicity of amifostine against the anticancer drug fotemustine in the Drosophila somatic mutation and recombination (SMART) test

Abstract

Amifostine (WR-2721), a phosphorylated aminothiol pro-drug, is a selective cytoprotective agent in normal tissue against the toxicities associated with chemotherapy and irradiation. Fotemustine is a cancer chemotherapeutic agent that belongs to an extremely active class of alkylating compounds. Amifostine was tested for antimutagenicity against fotemustine in the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Third-instar larvae that were trans-heterozygous for the two genetic markers mwh and flr were treated at different concentrations (2, 4, and 8 mu g/ml for fotemustine and, 1, 2, and 4 mu g/ml for amifostine) of the test compounds; for the antimutagenicity study, 8 mu g/ml fotemustine plus 1 and 2 mu g/ml amifostine were tested. Fotemustine showed mutagenic and recombinagenic effects in both genotypes in the wing-spot test. Amifostine significantly reduced the mutagenic and recombinagenic effects of fotemustine.