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Effect of Chloroquine on Malignant Lymphoreticular and Pigmented Cells in Vitro¹

Departamento de Patologia, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia

The cytotoxic effect of chloroquine has been studied in lymphoid cells derived from a patient with malignant lymphoma of the Burkitt type and in cells derived from a Cloudman S91 mouse malignant pigmented melanoma. Cultures were examined by light and electron microscopy at selected intervals after drug exposure. Findings were compared with cytotoxic effects produced by chloroquine in humans and in animals in vivo and with cytological changes described in Chediak-Higashi, a syndrome with alterations in the pigmentary and lymphoreticular tissues. Severe cytotoxic effect of chloroquine was observed in both cell lines. Effects appeared earlier in lymphoma than in melanoma cells, but more lymphoma than melanoma cells survived the toxic action. Effective toxic dose of the drug was about 30 µg/ml for lymphoma cells and about 20 µg/ml for melanoma cells. Common cytological changes in both strains of cells were nucleolar condensation with mild segregation of nucleolar components, clumping or margination of chromatin leaving a clear nucleoplasm, dilation of Golgi zone and endoplasmic reticulum, dilation and disruption of mitochondria, and presence of electron-dense whorls, autophagic vacuoles, myelin figures, and osmiophilic granules in the cytoplasm. The findings suggest that chloroquine labilizes cell membranes. The effect of chloroquine on melanin pigment was not clear. Similarities were found among the cytotoxic chloroquine-induced alterations described in vivo, the cytological alterations in Chediak-Higashi syndrome, and in our studies in vitro.

¹ This investigation was supported by a fellowship from the Anna Fuller Fund.

² Visiting Scientist in the Laboratory of Pathology, National Cancer Institute, Bethesda, Md. 20014, from 1966 to 1968.

Received 9/23/69. Accepted 11/12/69.