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)