The toxicity and selectivity of
3,4-dihydroxybenzylamine (DHBA), an experimental antimelanoma agent that cannot enter the
melanin pathway, broadly paralleled that of
L-dopa in a panel of human
melanoma cell lines sensitive or resistant to the latter
drug. A human
retinoblastoma cell line was found to be sensitive to both compounds. The toxicity and selectivity of both
catechols were associated with inhibition of
DNA synthesis; DHBA was more potent yet allowed a much greater degree of recovery compared with an equitoxic level of
dopa.
Dopa and DHBA had similar, dose-dependent effects on the cell cycle, arresting cells in S phase at low doses and in G1 at high doses. Replication of the DNA virus adenovirus was found to be inhibited by both agents. There was no difference between sensitive and resistant cell lines in the
manganese or
copper/
zinc forms of
superoxide dismutase, or in
iron content and
iron-binding capacity.
Catechol toxicity was inhibited by the
hydrogen peroxide scavenging agents
pyruvate and methaemoglobin. Sensitivity to
catechols did not correlate with
melanin or
tyrosinase content, rate of incorporation of
tyrosine or
dopa, intracellular levels of
phenylalanine or
tyrosine, or binding of a new
monoclonal antibody directed against a melanosomal
protein. These results indicate that DHBA and
dopa exhibit selective toxicity for
neural crest tumor cells independently of the melanisation pathway and of the
superoxide scavenging system.