Cytotoxicity of tamoxifen in normal and tumoral cell lines and its ability to induce cellular transformation in vitro.
Tamoxifen (TAM) is a non-steroidal anti-estrogen used to treat patients with estrogen receptor-positive breast cancer and as a chemopreventive agent against breast cancer in high risk pre- and post-menopausal women. However, recent studies have shown that tamoxifen causes endometrial and hepatic cancer. In this study, we examined the effects of tamoxifen (5, 10, 25 and 50 microM) on the growth and proliferation of nine tumoral cell lines (UACC62, MCF-7, NCI-460, K-562, OVCAR-03, PC-03, HT-29, 786-0, NCI-ADR) and non-tumoral cell lines (3T3, V79, MDCK, VERO). Chinese hamster lung fibroblasts (V79) were the most sensitive lineage to tamoxifen, with 21.6% of the cells showing apoptosis at 50 microM TAM. Microscopic analysis showed that, the cellular transformation caused by TAM in V79 cells was similar to that seen with 7,12-dimethylbenz(a)anthracene, thus indicating the carcinogenicity of TAM.
Petinari
Leandro
L
Department of Cell Biology, Institute of Biology, State University of Campinas, (UNICAMP), P.O. Box 6109, ZIP Code 13084-971, Campinas, SP, Brazil. leopet@unicamp.br
Kohn
Luciana Konecny
LK
de Carvalho
João Ernesto
JE
Genari
Selma Candelária
SC
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity*; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor / Q000648:ultrastructure; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D004965:Estrogen Antagonists / Q000633:toxicity*; D005260:Female; D006801:Humans; D013629:Tamoxifen / Q000633:toxicity*
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D013629:Tamoxifen