ABSTRACT
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Clomiphene/toxicity , Lymphocytes/drug effects , Mutagens/toxicity , Selective Estrogen Receptor Modulators/toxicity , Adult , Cell Division/drug effects , Cells, Cultured , Female , Humans , Lymphocytes/cytology , Sister Chromatid Exchange , Young AdultABSTRACT
In this study, we aimed at determining possible genetic damage to women who were exposed to in vitro fertilization (IVF) due to infertility with male factor. Four different genotoxicity tests were used in human lymphocytes in this study with regard to chromosomal aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), and comet tests. There was a statistically significant increase in sister chromatid exchange (SCE) test in the study group compared with the control group. In addition, a higher rate of MN frequency was determined only in the 2130 age range study group compared with the control group in the same age range. On the other hand, MN frequency did not differ significantly between the control and total study groups. In addition, there was no significant difference between the control group and the study group in terms of mitotic (MI), replication (RI), and nuclear division (NDI) indices. Furthermore, there was no statistically significant increase for chromosomal aberration and DNA damage to the study groups. Our results showed that in vitro fertilization treatments have a weak risk at the genetic level in cultured human lymphocytes.
Subject(s)
Fertilization in Vitro/adverse effects , Infertility, Female/genetics , Infertility, Male/genetics , Mutation/drug effects , Adult , Aging/physiology , Chromosome Aberrations/drug effects , Comet Assay , DNA Damage , Female , Humans , Lymphocytes/drug effects , Male , Micronucleus Tests , Mitotic Index , Mutagenicity Tests , Sister Chromatid Exchange/drug effects , Young AdultABSTRACT
The genotoxic potential of the vaccine adjuvant Squalene was assessed by the chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronucleus (MNs) tests in human lymphocytes and comet assay in both human and rat lymphocytes. Five different concentrations of squalene (1250-20,000 µg/ml for human lymphocytes and 0.07-1.12 mg/kg for rat lymphocytes) were studied. Squalene did not affect the CAs and MN frequency, in all treatments in vitro. A significant increase in SCEs was observed in almost all concentrations at 24 h treatment. Squalene did not affect significantly the comet tail length (CTL) (except 2500 µg/ml) and comet tail intensity (CTI) at all treatments in vitro. In rats, squalene significantly increased and decreased CTL and CTI in some doses. Although there are increasing and reduction in the effect, squalene cannot be regarded as genotoxic in human lymphocytes. However, further in vivo studies are required to be sure on the effect.
Subject(s)
Adjuvants, Immunologic/adverse effects , DNA Damage/drug effects , Squalene/adverse effects , Adult , Animals , Chromosome Aberrations/drug effects , Comet Assay , Dose-Response Relationship, Drug , Female , Humans , Lymphocytes/drug effects , Male , Micronucleus Tests , Rats , Rats, Wistar , Sister Chromatid Exchange/drug effects , Young AdultABSTRACT
In this study, the genotoxic effects of sodium benzoate (SB) and potassium benzoate (PB) were investigated in cultured human peripheral lymphocytes using chromosomal aberrations (CA), sister chromatid exchange (SCE), and micronuclei (MN). The level of nuclear DNA damage of SB and PB were also evaluated using the comet assay. The lymphocytes were incubated with different concentrations of SB (6.25, 12.5, 25, 50, and 100 µg/ml) and PB (62.5, 125, 250, 500, and 1000 µg/ml). A significant increase was observed in CA, SCE, and MN, in almost all treatments compared to negative controls. SB and PB significantly decreased the mitotic index (MI) in all the treatments, compared to the negative controls. However, neither of the additives affected the replication index (RI). Although SB significantly increased DNA damage, PB did not cause a significant increase in DNA damage. The present results indicate that SB and PB are clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro.
