The antimalarials quinacrine and chloroquine potentiate the transplacental carcinogenic effect of ethylnitrosourea on ependymal cells.
Quinacrine and chloroquine, two widely used antimalarials, bind strongly to deoxyribonucleic acid, thus preventing mutagenesis. We studied a possible chemoprotective effect of these substances on carcinogenesis of the nervous system induced in Wistar rats by transplacental administration of ethylnitrosourea. One experimental group consisted of rats born from mothers treated with quinacrine prior to prenatal exposure to ethylnitrosourea; a second group consisted of rats chronically treated with chloroquine after prenatal exposure to ethylnitrosourea. When compared with controls, no significant differences were observed in tumor incidence. However, early tumor growth was observed in both rats treated with quinacrine (P < 0.0004) and rats treated with chloroquine (P < 0.02). These differences were due mostly to rapid development of ependymomas of the spinal cord. Our results suggest that quinacrine and chloroquine do not prevent the structural alterations induced in DNA by ethylnitrosourea, which lead, in the long term, to a high incidence of neoplasms in the nervous system. Moreover, the antimalarials studied seem to promote the carcinogenic effects of ethylnitrosourea on ependymal cells.
Reyes
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Neuroimmunology Unit, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. jsotelo@servidor.unam.mx
Rembao
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Sotelo
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D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D001932:Brain Neoplasms / Q000139:chemically induced*; D002273:Carcinogens / Q000633:toxicity*; D002738:Chloroquine / Q000633:toxicity*; D004357:Drug Synergism; D004805:Ependyma / Q000166:cytology / Q000187:drug effects*; D004806:Ependymoma / Q000139:chemically induced*; D005038:Ethylnitrosourea / Q000633:toxicity*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007124:Immunoenzyme Techniques; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011796:Quinacrine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013120:Spinal Cord Neoplasms / Q000139:chemically induced*; D016708:Synaptophysin / Q000032:analysis
D000962:Antimalarials; D002273:Carcinogens; D005904:Glial Fibrillary Acidic Protein; D016708:Synaptophysin; D002738:Chloroquine; D011796:Quinacrine; D005038:Ethylnitrosourea