Some Genetic Changes in Lymphocytes and Bone Marrow Cells Associated with Yasmin Contraceptive Pills, Cafergot and Wild Carrot Seeds Oil in Women and Mice

           This study was undertaken to figure out the effects of contraceptives pills "Yasmin", fungal alkaloids "Cafergot" and wild carrot seed oil on apoptosis, DNA damage (using comet assay), cytogenetic analysis (using micronucleus assay) in blood lymphocytes of mice as well as on  pregnancy rate of female mice. The oral effects of contraceptive pills (Yasmin) on apoptosis, DNA damage, cytogenetic analysis and aromatase activity of women blood lymphocytes were also investigated. Thirty five mice were divided into seven groups in antifertility experiment (3 females and 2 males per each group). The first group was regarded as a negative control group treated with normal saline, whereas groups II and III were treated with 30 and 60 µg/kg of contraceptive pills (COCPs) respectively. Groups IV and V were treated with 10 and 20 µg/kg of Cafergot pills respectively, and  groups VI and VII were treated with 0.05 and 0.1 ml of wild carrot seed oil respectively. The pregnancy rate was higher (P≤0.01) in control and group IV as compared with the other groups. In apoptosis experiment, fifteen mice were used and divided into five equal groups. The first group was regarded as a control, while the second positive group was treated with 50 µg/kg of methotrexate (MTX). The remaining three groups were orally treated with 60, 20 µg/kg and 0.1 ml of COCPs, Cafergot and wild carrot seed oil respectively. The treatments were given for 5 successive days. Lower (P≤0.05) apoptotic percentage was observed in wild carrot seed oil that equal to the negative control group, whereas higher (P≤0.05) percentage was noticed in the MTX group, indicating that COCPs group is the most inducing contraceptive agents. Higher (P≤0.05) viable cells were noticed in Cafergot (99.54%) and wild carrot seed oil (99.6%) being similar with negative control (99.66%) and greater than COCPs (97.83%) and MTX group.  In comet assay, the same groups were used as mentioned in apoptotic experiment. Significant (P≤0.05) differences were observed among groups
in tail length, being taller in MTX group (17.5%), followed by COCPs (12.18%) and lower in wild carrot seed oil group (1%). The percentage of DNA in the tails were 15.08% in COCPs while in Cafergot and wild carrot seed oil were 6.18% and 0.22% respectively. In control the percentage of DNA in the tails were 1.09% and 19.14% in MTX group. The tails moments for the exposed group with contraceptive pills were 25.04%, while in Cafergot and wild carrot seed oil were 5.09% and 0.36% consequently. In micronuclei investigating experiment, the wild carrot seeds oil and Cafergot recorded less (P≤0.05) percentage as compared with other groups being 2.75% and 3.5% respectively. In contrast, MTX recorded greater (P≤0.05) percentage of micronuclei namely 14.5% followed by COCPs group 10.75%. The percentage of apoptosis in women used Yasmin contraceptive pills were  7.08 and  12.2%  for 2-5  and 6-8 years respectively as compared with the negative control (0.18%). Higher (P≤0. 05) viable cell percentage
was noticed in negative control (99.54%) as compared contraceptive pill groups either for 2-5 years (92.18%) and 6-8 years (86.84%). The average tail lengths of comet in women used Yasmin pills were 19.13 and 25.08% for women used Yasmin pills for 2-5 and 6-8 years respectively and different (P≤0.05) from those in control group (0.8%). Furthermore, the percentage of DNA in comet tail were 20.12 and  28.63% for of women used Yasmin pills for  2-5 and 6-8 years respectively, being  different (P≤0.05) from those in control group (1.6%). The tail moments of comet were 23.63 and 31.81% in women used Yasmin pills for 2-5 and 6-8 years respectively, being different (P≤0.05) from those in control  women (0.01%). The average numbers of micronuclei were 0.016 and 0.021%  for women used Yasmin pills from 2-5 and 6-8 years respectively, seems higher (P≤0.05) than those in control group (0.004%). The negative control group of women exhibited the highest levels (9.303%) of aromatase activity in comparison with Yasmin pills groups used for  2-5 (6.113% ) and 6-8 (5.248%) years. In conclusion, Yasmin pills was the most inducing drugs for apoptosis and DNA damage  in comparison with Cafergot and carrot seed oil.