Effect of clozapine on human sperm chromosomes in vitro

Huaqing MENG

ABSTRACT

BACKGROUND:

Clozapine is a common antipsychotic drug for treating psychotic patients. Some reports suggest that it can cause chromosomal aberration of human cells. This study was designed to analyze the effect on mutagenesis of human generative cells and genetics toxicity of generative cells.

OBJECTIVE:

To research the effect of clozapine on human sperm chromosome with testing system ex vivo.

DESIGN:

Randomized controlled observation on the basis of human sperm chromosome.

SETTING:

Center of Psychological health, the First Hospital affiliated to Chongqing Medical University.MATERIALS Human sperm was selected from healthy adult males who were not received mutagenesis factors within half a year. Clozapine was provided by the Ninth Pharmaceutical Factory of Shanghai. Ovum was selected from female golden shrewmouse aged 6-8 weeks. Ovum was fertilized and washed with BWW culture medium containing 0.3% or 3.5% human serum albumin. After fertilization, ovum was cultured with ovi-culture medium containing 10% serum of shrewmouse.

METHODS:

At three days before experiment, shrewmouse was muscularly injected with 40 unit/ampoule preganat mares esrum gonadotrophin, and then with 30 unit/ampoule human chorionic gonadotrophin. Semen was maintained in aseptic beaker and made 5 mL sperm suspension after washing, centrifugation and capacitation. The suspension was equally put into 5centrifuged tubes. 40 mg/L bleomycin A5 was added into one tube to regard as positive control, one tube was regarded as negative control without adding any reagent, and other tubes were added with clozapine at the concentrations of 200, 400 and 800 μg/L, respectively. Ovarium mound cells and pellucid zone in ovum were wiped out with 0. 1% alidase and pancreatin, and then, equally transplanted into a blank gutta in five culture medium. Sperm chromosome was established with stepped fixed air technique.MAIN OUTCOME

MEASURES:

Sperm rate and broken amount of chromosomal structural aberration.

RESULTS:

When concentration of clozapine was at 200, 400 and 800 μg/L,respectively, sperm rate and broken amount of chromosomal structural aberration were not significantly different from those in blank control group, and there was also no significant difference among three concentration groups. However, there was significant difference between 40 mg/L bleomycin A5 group and negative control group (P ＜ 0.01).

CONCLUSION:

Clozapine cannot damage human sperm chromosome through detecting the effect of mutagen on breakage of chromosome with testing system ex vivo, but it has other genetics toxic mechanisms on human sperm chromosome.