الفهرس 
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Abstract
This experiment was carried out to study a model of drug-drug interaction in inducing genotoxicity by administration of Ivermectin (antiparasitic drug and P-gp substrate) and erythromycin (antibiotic and P-gp inhibitor) in a short term administration for two weeks and long term exposure for 8 weeks by measuring incidence of chromosomal aberration, micronucleus frequency (MN), mitotic index (MI) and detecting DNA fragmentation by RAPD-PCR.
1. Short-term experiment (2 weeks):
Twenty Swiss albino male mice were allotted into four groups
• Group 1: Control group mice kept without any treatment.
• Group 2: mice were injected intra-peritoneal by ivermectin, (Paramectin) (300 µg/kg b. wt.) once a week.
• Group 3: mice were orally administered with erythromycin daily for 2 weeks (40 mg/kg b. wt.).
• Group 4: mice were orally administered with erythromycin (40 mg/kg b. wt.) then after one hour injected intra-peritoneal by ivermectin (300 µg/kg b. wt.).
2- Long-term experiment (8 weeks):
where the same experimental design of the short term experiment was applied with increasing the period of experiment to 8 weeks.
The animals were subjected to the following assesments:
І. Cytogenetic studies:
The effects of administration of ivermectin either alone or simultaneously with erythromycin on chromosomes and subsequently on DNA through presence of strucrual chromosomal aberration represented by fragments, stickiness and deletions or numerical chromosomal aberrations as polyploidy. Also, detecting frequency of micronucleus and rate of mitotic index in bone marrow cells.
The obtained results were:
1- Administration of both ivermectin and erythromycine are capable of inducing genotoxic effects represented by producing chromosomal aberration after 2 or 8 weeks. The most prominent types of aberration were fragment and stickiness. While ivermectin alone showed some genotoxic effect by inducing chromosomal aberration after short term administration.
2- Concerning micronucleus test after 2 weeks of treatment ivermectin is shown to produce higher frequency of micronucleus while after 8 weeks both combinations of drugs induced higher the rate of micronucleus frequency.
3- By observing the mitotic activity ivermectin has no effect on mitotic activity after 2 or 8 weeks although both combinations of drugs caused marked reduction in mitotic activity after 2 weeks.
ІІ. Molecular studies
Ten primers were used for short and long term exposure experiments only 2 primers gave PCR products, OPA4 and OPA40 both primers were used for short and long term exposure experiment.
Variations in the banding pattern were observed between different treatments. The groups which receive both combinations of drugs have a higher number of bands compared with other groups. The analysis of data showed the relationship between treated animals with ivermectin, erythromycin and combination of both drugs compared to the control. Different polymorphic profiles were obtained in different groups in RAPD-PCR. Variations within the individuals of each group were also observed. Clustering of the treated groups indicate their similarity compared with the control.
On conclusions, using both ivermectin and erythromycin has obvious genotoxic effect represented by inducing changes on level of chromosome (structural chromosomal aberrations) subsequently induced changes at level of DNA.