genotoxic potential of nicotine in adult male albino rats with special reference to the protective role of alpha - tocopherol

The present study was under taken to reveal the toxic effects of nicotine - the main active principle in tobacco - on cell chromosomes and peripheral blood cells of adult male albino rats. Also to detect histological changes in bone marrow cells. Furthermore, the protective effect of the antioxidant vitamin E [alpha - tocopherol] in nicotine toxicity was studied. The study was carried out on one handered and twenty adult male albino rats divided into six numerically equal groups. The first group was the negative control group. The second was injected with distilled water, the solvent of nicotine, daily by intraperitoneal [IP] injected. The third group was given corn oil, the solvent of vitamin E, daily by gavage. The fourth group was given alpha - tocopherol daily by gavage. The fifth group was the nicotine group where it was injected intraperitoneally daily. Lastly the sixth group was given daily both nicotine by [IP] injections and alpha - tocopherol by gavage. The duration of the experiment was eight weeks. Twenty four hours after the end of the experiment each group was divided into two subgroups. Chromosomal study was carried out on the first subgroup bone marrow cells of rats. Five hundred cells in the mitotic stage were studied in each group. Any numerical or structural chromosomal abnormality was recorded. The 2nd subgroup was anaesthetized, blood samples were taken from each rat to study total and differential blood count. At the same time samples were taken from bone marrow of the femora and kept in preservative. Paraffin sections were prepared from bone marrow samples and stained either by haematoxylin and eosin of Feulgin stain to be studied by light microscope. For samples which were studied by electron microscope, ultrathin sections were stained by lead citrate and uranyl acetate. The results were statistically analysed. The study had revealed significant difference in the chromosomal structure and number in the nicotine group compared to the control groups. This was in the form of a significant increase in the number of cells with hyperdiploid or hypodiploid number of chromosomes and a significant increase in the rate of appearance of ring chromosome, break, fragments and gaps. Meanwhile, complete blood count revealed a significant decrease in total and differential blood count in the nicotine group, mainly as a decrease in the lymphocytic count. Furthermore, the light microscopic examination revealed a significant decrease in the number of bone marrow cells. Also a decrease in nuclear DNA content of the nucleated blood cell precursors was detected. As regard the electron microscopic examination most of the nucleated blood cell precursors showed disrupted cell membrane and nuclei were pyhnotic in the nicotine group. On the other hand, the nicotine and vitamin E combination group revealed a statistically significant improvement in the number and structure of the chromosomes and the total different blood cell count. At the same time the histological picture was improved both by light and electron microscopic examination where the DNA content of the cell was nearly normal and most of the cells appeared with intact cell membrane. The nuclei of the cells appeared as heterogenous structures with electron - dense and electron - lucent areas. This study has revealed the protective role of the antioxidant vitamin E [alpha - tocopherol] which proved the role of nicotine in forming free radicals that affect the cell. Moreover this study must be followed by other studies to prove the protective role of vitamin E in human smokers