ELSEVIER Mutation Research 305 (1994) 145-150 Fundamentaland Molecurar Mechanisms of Mutagenesis The anticlastogenic effect of tocopherol in peritoneal macrophages of benznidazole-treated and ovariectomized mice Zulmira G.M. Lacava *, Helena Luna Department of Genetics and Morphology, Institute of Biological Sciences, Universityof Brasilia, 70910-900 Brasilia, DF, Brazil (Received 12 January 1993) (Revision received 8 August 1993) (Accepted 1 September 1993) Abstract Cytogenetic studies revealed a significant increase in the frequency of structural chromosome aberrations of peritoneal macrophages from hyperimmune Swiss mice after ovariectomy. The administration of the nitroarene benznidazole caused a large number of chromosomal deletions in peritoneal macrophages of sham-ovariectomized animals. The clastogenic effect of benznidazole was much greater in peritoneal macrophages of ovariectomized mice. The anti-oxidant a-tocopherol protected the peritoneal macrophages from developing ovariectomy- or benznidazole-induced chromosomal aberrations, thus suggesting free radical damage in these processes. Key words: Benznidazole; Cytogenetic damage; Anticlastogenic eftect; Macrophage; Ovariectomy 1. Introduction Benznidazole (BZ) is a nitroarene compound used in the treatment of Chagas' disease (American trypanosomiasis)caused by Try- panosoma cruzi. It has been shown that BZ is mutagenic in bacteria (Nagel and Nepomnaschy, 1983; Ohnishi et al., 1983) and clastogenic in T. cruzi (Gouman et al., 1985). Induction of chromo- somal aberrations and micronuelei and an in- crease in the frequency of expression of fragile sites were reported in cultures of peripheral blood lymphocytes from chagasic children treated with * Corresponding author. BZ (Gorla et al., 1988; Moya and Trombotto, 1988) or in bone marrow cells of mice treated with the drug (Navarro et al., 1984). Although the mechanisms of BZ induction of chromosomal aberrations have not been deter- mined, it has been shown that this trypanocidal nitroarene undergoes enzymatic reduction of the nitro group and generates free radicals such as nitro anions, hydroxyl, singlet oxygen and hydro- gen peroxide (Docampo et al., 1971; Moreno et al., 1982). The free radicals are known to cause DNA alterations such as base damage, single- and double-strand breaks, cross-linking, chromo- somal aberrations (Sun, 1990) and peroxidative damage to membrane lipids (Chow, 1991). How- ever, the deleterious action of some free radicals might be prevented by anti-oxidants. In this con- 0027-5107/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0027-5107(93)E0183-Q