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In vitro and in vivo tests in humans confirm that the antimalarial drug mefloquine is not mutagenic

Cesar Koppe Grisolia^I; Catarina Satie Takahashi^II; Iris Ferrari^I

^IDepartamento de Genética e Morfologia, Instituto de Biociências, Universidade de Brasilia, 70910-900 Brasilia, DF, Brasil. Send correspondence to C.K.G.
^IIDepartamento de Biologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14049-901 Ribeirão Preto, SP, Brasil

ABSTRACT

The antimalarial drug mefloquine has till now only been evaluated for mutagenicity using nonhuman systems. In the present study, mefloquine was tested in human lymphocytes in vitro for chromosomal aberrations (C.A.) and sister chromatid exchanges (SCE), and in human lymphocytes in vivo from patients under mefloquine antimalarial therapy living in the Amazon gold panning areas (Brazil). The data show a decrease in mitotic index at the highest concentration (12 mg/ml), representing a cytotoxic effect in the in vitro treatment, for both 48- and 72-hour cultures. From the results obtained from in vivo human therapy, it can be concluded that this compound induces a significant decrease in lymphocyte proliferation, also found in vitro. In both situations, mefloquine did not show any evidence of an increase in C.A. and SCE in human lymphocytes.

Keywords: antimalarial drug; mefloquine; mutagenic.

REFERENCES

Davidson, M.W., Griggs Jr., B.G., Boykin, D.W. and Wilson, W.D. (1975). Mefloquine, a clinically useful quinolinemethanol antimalarial which does not significantly bind to DNA. Nature 254: 632-634.

Desjardins, R.E., Pamplin III, C.L., von Bredow, J., Barry, K.G. and Canfield, J. (1979). Kinetics of a new antimalarial, mefloquine. Clin. Pharmacol. Ther. 26: 372-379.

Grisolia, C.K. and Takahashi, C.S. (1994). Assessment of antimalarial drugs chloroquine and mefloquine with NaNO2 and HgCl2 in rodents. Mutat. Res. 305: 151-156.

Korenberg, J.R. and Freedlender, E.F. (1974). Giemsa technique for detection of sister chromatid exchanges. Chromosoma 48: 355-360.

Krogstad, D.J., Guzman, I.Y., Kyle, D.E., Oduola, A.M.J., Martin, S.K., Milhous, W.K. and Schlesinger, P.H. (1987). Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance. Science 238: 1283-1285.

Martin, S.K., Oduola, A.M.J. and Milhous, W.K. (1987). Reversal of chloroquine resistance in Plasmodium falciparum by verapamil. Science 235: 899-901.

Moorhead, P.S., Norwell, P.C., Mellman, W.J., Batipps, D.M. and Hungerford, D.A. (1960). Chromosome preparation of leukocyte culture from human peripheral blood. Exp. Cell Res. 20: 613-616.

Perry, P. and Wolff, S. (1974). New giemsa method for the differential staining of sister chromatid exchanges. Nature 251: 156-158.

Rozman, R.S. and Canfield, C.J. (1979). New experimental antimalarial drug. Adv. Pharmacol. and Chemotherapy 16: 1-43.

Schupbach, M.E. (1979). Mutagenicity evaluation of the two antimalarial agents chloroquine and mefloquine, using a bacterial fluctuation test. Mutat. Res. 68: 41-49.

Threnholme, G.M., Williams, R.L., Desjardins, R.E., Frischer, H., Carson, P.E. and Rieckmann, K.H. (1975). Mefloquine WR 142,490 in the treatment of human malaria. Science 235: 792-794.