17beta-estradiol, diethylstilbestrol, tamoxifen, toremifene and ICI 164,384 induce morphological transformation and aneuploidy in cultured Syrian hamster embryo cells.
To examine the ability of estrogens and anti-estrogens to induce cellular transformation and genetic effects, Syrian hamster embryo (SHE) cells were treated with estrogens, 17beta-estradiol (E2) or diethylstilbestrol (DES), or with anti-estrogens, tamoxifen (TAM), toremifene (TOR) or ICI 164,384. Treatment with each substance for 1-3 days suppressed cellular growth in a dose-dependent manner. Colony-forming efficiency (CFE) increased following treatment of cells with E2 or DES for 48 hr at 3 or 10 microM but decreased at 20 or 30 microM. In contrast, CFE was increased by treatment with TAM, TOR or ICI 164,348 over the concentration range examined (1-30 microM). Treatment with each chemical at 1-30 microM for 48 hr caused morphological transformation of SHE cells in a dose-related fashion. The highest frequency was exhibited in SHE cells treated with DES at 20 microM and was 2 times higher than that induced by treatment with benzo[alpha]pyrene (B[alpha]P) at 4 microM. Transformation frequencies induced by other substances (E2, TAM, TOR and ICI 164,348) did not exceed that induced by the B[alpha]P treatment. TOR showed a higher transforming ability over all concentrations examined when compared to the other anti-estrogens (TAM and ICI 164,348). No significant increases in the frequencies of chromosomal aberrations were observed in SHE cells that were treated with any of the chemicals. However, treatment of SHE cells with each chemical induced a dose-dependent increase of aneuploid cells in the near diploid range. Our results indicate that the ability of the estrogens and anti-estrogens to induce numerical chromosomal abnormality may be involved in their cell transformation activity and potential carcinogenicity.
Tsutsui
T
T
Department of Pharmacology, The Nippon Dental University, Tokyo, Japan.
Taguchi
S
S
Tanaka
Y
Y
Barrett
J C
JC
D000782:Aneuploidy; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts; D004054:Diethylstilbestrol / Q000494:pharmacology / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000166:cytology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000633:toxicity; D008647:Mesocricetus; D015394:Molecular Structure; D053284:Polyunsaturated Alkamides; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000494:pharmacology / Q000633:toxicity*; D017312:Toremifene / Q000494:pharmacology / Q000633:toxicity*
D018736:DNA Adducts; D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen; D001564:Benzo(a)pyrene; D004958:Estradiol; D004054:Diethylstilbestrol; D017312:Toremifene; C051781:ICI 164384; D004247:DNA