We demonstrated the presence of inducible and endothelial nitric oxide synthases in histiocytic lymphoma U937 cells by staining with anti-iNOS and anti-eNOS antibodies. We also investigated the effects of retinol and retinoic acid on nitric oxide production by both U937 cells and ZR-75-1 human breast cancer cells. U937 cells which had been treated with either retinol or retinoic acid (10-10-10-6 M) exhibited no significant difference in nitric oxide secretion into conditioned medium. Conversely, for ZR-75-1 cells, both retinol and retinoic acid (10-10-10-6 M) caused a significant (p<0.001) increase in the amount of nitrite secreted. Our results indicate that retinoid induced growth inhibition of breast cancer cells is associated with an increase in NO production, however, an increase in NO synthesis does not mediate retinoid induced differentiation of U937 cells.

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