Induction of sister chromatid exchanges and cell division delays by clomiphene citrate in human lymphocytes.

Abstract

Clomiphene citrate (CC) is a selective estrogen receptor modulator and is used for the treatment of in vitro fertilization, intracytoplasmic sperm injection, intrauterine insemination, and so on. In this study, sister chromatid exchanges (SCEs) and cell cycle delays were analyzed to investigate genotoxicity and cytotoxicity of CC in peripheral blood lymphocytes of healthy women. Human peripheral blood lymphocytes obtained from two donors were used to detect genotoxicity and cytotoxicity of CC. Lymphocytes were treated with various concentrations (0.40, 0.80, 1.60, and 3.20 µg/ml) of CC. A negative (distilled water) and a positive control (mitomycin-C = 0.20 µg/ml) were also used simultaneously with test substance-treated cultures. SCEs and cell division delays were measured from 25 cells and 100 cells perdonor, respectively. CC significantly increased the mean SCE value at all concentrations compared with the negative control. This increase was found to be dose dependent (r = 0.83) and at the highest concentration, nearly two times higher increase was observed than the negative control. However, replication index was not affected by the CC treatment. The present study shows that CC is genotoxic for human lymphocytes in vitro. Further investigations, especially in vivo are now needed in different test organisms to clarify the genotoxic activity of CC, which should also help to better understand genotoxic mechanism of this ovulation-stimulating drug.