In vivo evaluation of the genotoxic effects of clomiphene citrate on rat reticulocytes: a micronucleus genotoxicity.
OBJECTIVE
To determine the genotoxic effects of clomiphene citrate (CC) on rat reticulocytesin vivo.


METHODS
In this prospective, randomized, controlled study, rats were each assigned randomly to the CC 50, CC 100, CC 200, or control group and were given repeat doses of 0.16, 0.32 or 0.64 mg CC, or normal saline, respectively. Each study group received its CC dose in 2 ml of saline intraperitoneally for 5 days, while the control group received only 2 ml of saline. Each treatment cycle was repeated six times. Six months later, the rats were euthanized. Bone marrow tissues were removed, and pluripotent reticulocyte cells with micronuclei, nuclear buds, and binuclear abnormalities were analyzed using an in situmicronuclei assay under light microscopy. The proportion of micronucleated erythrocytes was measured.


RESULTS
Fewer cells with nuclear buds and binuclear abnormalities were detected in the CC 50 group and controls. The CC 100 and 200 groups had significantly (p < 0.05) more nuclear buds and binuclear abnormalities compared with the CC 50 group and controls in the cytogenetic analysis of bone marrow stem cells.


CONCLUSIONS
In rats, the micronucleus genotoxicity assay suggests a dose-dependent CC effect on genomic instability in bone marrow stem cells in vivo.
Duran
Bulent
B
Department of Obstetrics and Gynecology, Cumhuriyet University, Faculty of Medicine, Sivas, Turkey.
Ozdemir
Ismail
I
Demirel
Yeltekin
Y
Ozdemir
Ozturk
O
Cetin
Ali
A
Guven
Aysel
A
D000818:Animals; D002996:Clomiphene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005300:Fertility Agents, Female / Q000633:toxicity*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D051381:Rats; D017208:Rats, Wistar; D012156:Reticulocytes / Q000187:drug effects* / Q000473:pathology*; D013234:Stem Cells / Q000187:drug effects
D005300:Fertility Agents, Female; D002996:Clomiphene