In two-thirds of studies on the effect of genistein-containing soy mat
erials in animal models of cancer, the risk of cancer (incidence, late
ncy or tumor number) was significantly reduced. In addition, purified
genistein delayed mammary tumor appearance in association with increas
ed cell differentiation in mammary tissue in rats treated with 7,12-di
methylbenz[a]anthracene when administered neonatally, inhibited phorbo
l ester-induced H2O2 production in a model of skin cancer, and inhibit
ed aberrant crypt formation in a model of colonic cancer. In in vitro
models, genistein inhibited the proliferation of human tumor cell line
s in culture with a wide variation in IC50 values (2.6-79 mu mol/L, or
1-30 mu g/mL). In only a few cases was the IC50 below 13.2 mu mol/L (
5 mu g/mL), the presumed upper limit for the serum genistein concentra
tion in those on a high-soy diet. In future studies, greater emphasis
should be placed on the effect of genistein on nontransformed, normal
cell lines from the tissues where cancer can occur rather than establi
shed tumor cell lines. Similarly, the effect of genistein on the progr
ession and/or promotion of cancer may be more clearly examined using n
ontransformed cell lines transfected with specific oncogenes thought t
o be activated during oncogenesis.