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Genistein-induced cell differentiation and protein-linked DNA strand breakage in human melanoma cells.

Genistein, an in vitro inhibitor of topoisomerase II and tyrosine kinases, elicited an inhibition of growth and increased melanin content in five human melanoma cell lines, after six days of treatment at a concentration of 45 microM. In two lines examined more thoroughly, HO and SK-MEL-131, treatment with genistein also increased other markers of differentiation, including tyrosinase activity, reactivity with CF21 monoclonal antibody, and dendrite-like structure formation. The genistein-evoked increases in melanin content and tyrosinase activity were concentration- and time-dependent. Treatment of HO and SK-MEL-131 cells with 45 microM genistein for 24 hr or 60-600 microM genistein for only 1 hr resulted in an increase in protein-linked DNA strand breaks. Our results suggest an association between the genistein-evoked, protein-linked, DNA strand breaks and the genistein-induced differentiation of human melanoma cells.