Specificity of growth inhibition of melanoma by 4-hydroxyanisole.

An experimental study using human melanoma (NEL-MI), rat hepatoma (Fu5-5), and human kidney (293-31) cell lines was undertaken in order to evaluate the antitumor activity of 4-hydroxyanisole (4-OHA) in vitro. Prior reports have indicated highly specific antitumor activity of 4-OHA against melanoma cells in vitro. This specific antitumor activity has been proposed to be due to the oxidation of 4-OHA by tyrosinase to cytotoxic oxidation products. Dose-dependent cytotoxicity was observed when cells were cultured for 72 h in the presence of 4-OHA. At 100 microM, 4-OHA produced growth inhibition of 62%, 32%, and 55% in melanoma, hepatoma, and kidney cell lines, respectively. No effect was seen at 10 microM 4-OHA. 1,000 microM 4-OHA produced 100% kill. Tyrosinase activity was detected only in melanoma cells. The effect of 100 microM 4-OHA on the incorporation of 3H DNA precursors in melanoma, hepatoma, and kidney cells was also studied. Thymidine incorporation was inhibited in all three cell lines at the lowest cell density tested, with the greatest inhibition seen on melanoma cells. As cell density increased, the effect of 4-OHA on thymidine incorporation decreased. With respect to RNA synthesis, 4-OHA significantly reduced the incorporation of uridine in all three cell lines, with the greatest effect in melanoma cells. Cell density also affected the inhibition of uridine incorporation, but to a lesser extent than that observed on thymidine incorporation. The effect of 4-OHA on leucine incorporation was modest and uninfluenced by cell density. Thus, cytotoxicity of 4-OHA may involve two different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombotic thrombocytopenic purpura.

This serious disorder of young adults is characterized by fever, hemolytic anemia, hemorrhagic signs, various neurologic abnormalities and renal dysfunction. Laboratory findings include a negative Coombs' test for hemolytic anemia, severe thrombocytopenia, and fragmented erythrocytes on the peripheral blood smear. Without treatment, mortality may exceed 80 percent. Early diagnosis and prompt therapy with high-dose corticosteroids and antiplatelet agents, as well as exchange plasmapheresis when indicated, bring about remission in 60 to 80 percent of patients.

Pulmonary carcinoid associated with a parathormone producing melanoma.

A rare presentation of hypercalcemia secondary to the probable ectopic production of parathormone by a malignant melanoma associated with a pulmonary carcinoid is discussed. We suggest the association of melanoma with multiple endocrine neoplasia.