Genotoxicity of Antiamebic, Anthelmintic, and Antimycotic Drugs in Human Lymphocytes
The use of amebicidal, anthelmintic, and antimycotic drugs in Mexico is widespread. Few studies have evaluated the mutagenic activity of the most commonly used antiparasitic drugs. Of these, the majority of the mutagenic evaluations have been conducted in microbial test systems and have yielded inconsistent results (1-5). Experiments in our laboratory using the Salmonella typhimurium microsomal test system have shown that niclosamide (anthelmintic) and dehydroemetine (amebicide) induce frameshift mutations following activation by microsomal enzymes (6). While neither chloroquine di phosphate (amebicide) nor ketoconazole (antimycotic) display mutagenic activity on the standard Ames test (unpublished observations for ketoconazole), the former induces frameshift mutations in the fluctuation test. Mutagenic activity has also been detected in the urine of mice treated with niclosamide (6). The capacity of chloroquine diphosphate to bind DNA is well documented (7) , and it has also been reported to induce clumping in nuclei, as well as to produce chromosomal abnormalities in a bone marrow cell line (8) . In view of these data we decided to evaluate the genotoxic effects produced in vitro in human lymphocytes, cultured with or without the addition of an auxiliary metabolic test system, by 4 antiparasitic drugs: chloroquine diphosphate, deyhdroemetine, niclosamide, and ketoconazole. Furthermore, we monitored chromosomal changes in lymphocytes of 2 patients treated chronically with ketoconazole.
KeywordsHuman Lymphocyte Mutagenic Activity Genotoxic Effect Sister Chromatid Exchange Microsomal Enzyme
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