Cell-transforming activity and mutagenicity of 5 phytoestrogens in cultured mammalian cells.
For the simultaneous assessment of in vitro carcinogenicity and mutagenicity of phytoestrogens, the abilities of 5 phytoestrogens, daidzein, genistein, biochanin A, prunetin, and coumestrol, to induce cell transformation and genetic effects were examined using the Syrian hamster embryo (SHE) cell model. Cellular growth was inhibited by all phytoestrogens in a concentration-related manner. The growth inhibitory effect of the compounds was ranked: genistein, prunetin > coumestrol > biochanin A > daidzein, which did not correspond to their apoptosis-inducing abilities. Morphological transformation in SHE cells was elicited by all phytoestrogens, except, prunetin. The transforming activities were ranked as follows: genistein > coumestrol > daidzein > biochanin A. Somatic mutations in SHE cells at the Na(+)/K(+) ATPase and hprt loci were induced only by genistein, coumestrol, or daidzein. Chromosome aberrations were induced by genistein or coumestrol, and aneuploidy in the near diploid range was occurred by genistein or biochanin A. Genistein, biochanin A or daidzein induced DNA adduct formation in SHE cells with the abilities: genistein > biochanin A > daidzein. Prunetin was negative for any of these genetic endpoints. Our results provide evidence that genistein, coumestrol, daidzein and biochanin A induce cell transformation in SHE cells and that the transforming activities of these phytoestrogens correspond to at least 2 of the mutagenic effects by each phytoestrogen, i.e., gene mutations, chromosome aberrations, aneuploidy or DNA adduct formation, suggesting the possible involvement of mutagenicity in the initiation of phytoestrogen-induced carcinogenesis.
Tsutsui
Takeki
T
Department of Pharmacology, The Nippon Dental University, School of Dentistry at Tokyo, Tokyo, Japan.
Tamura
Yukiko
Y
Yagi
Eiichi
E
Someya
Hitomi
H
Hori
Itsuro
I
Metzler
Manfred
M
Barrett
J Carl
JC
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D003375:Coumestrol / Q000494:pharmacology; D006224:Cricetinae; D018736:DNA Adducts; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D008647:Mesocricetus; D008677:Metaphase; D008956:Models, Chemical; D009153:Mutagens; D009154:Mutation; D048789:Phytoestrogens; D028321:Plant Preparations; D013997:Time Factors
D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D009153:Mutagens; D048789:Phytoestrogens; D028321:Plant Preparations; C083295:prunetin; C004742:daidzein; D019833:Genistein; C004541:biochanin A; D003375:Coumestrol