Several Compounds Induce Aneuploidy Mechanism Study

Physical ,chemical and biological factors which induce genetic damages in human are called genotoxin, such as mutagen,clastogen and aneugen, etc. Aneugen play a significant role in adverse human health conditions including birth defects,pregnancy wastage and cancer.It bring about a big problem on health ,social and economic issues. DNA, chromosome,cell membance ,spindle apparatus ,even the receptors and signal system are always the targets of aneugens.So,the present situation is that there are various endpoints and aneuploidy assays available. Unfortunately ,we known very little about the various causes and mechanisms of aneuploidy production. For human health protection,screening aneugic chemicals and exploring the aneuploidy- induction mechanisms is a forcing task of genetic toxicology. In this paper , several aneugens,antagonists to cholinergic receptors and activators or inhibitors of phosphatidylinositol signal pathway were selected.By analysing C mitosis effects, configuration of nucleus/cytoplasm and the level of the second messenger content in mammalian cells after treating with these chemicals,we discovered the aneugic potential and the mechanisms of aneuploidy-induction of selected chemicals.The procedures are:(1) In vitro and in vivo,we analysed C mitosis effects,frequency of binuclear cells and 5 configuration of nucleus/cytoplasm from chromosome separation to mitotic coordination and explored the mechanisms of aneuploidy- induction of antagonists to cholinergic receptors which includes AIR d-Tubocurarine (d-TUB),and Tripterygium hypoglaucum (level) Hutch (THH) ;(2)We also analysed the C梞itosis effects and measured diacylglycerol (DAG) contents of Chinese hamster V79 cells in vitro asynchronously after treating with THH, coichicine ( COL ) and hydroquinone ( HQ ) and explored the possible mechanisms of aneuploidy-induction. The results showed that (1) In mouse bone marrow cells, ATR induced significantly C桵 effects at high dose (5.2mg/kg) (P<0.00l桹.05); d- TUB increased the frequency of C mitosis cells only at low dose (0.063 mg/kg);THH (in treated groups) significantly induced C桵 effects(P<0.00l?.05) ; HQ induced C桵 effects at high dose ( 150mg/kg) (P抸O.01) and increased the frequency of C mitosis cells at used dose range (100?50 mg/kg) (P<0.0l). The results indicated that these chemicals has aneugenic potential. Results from the analysis of configuration of nucleus/cytoplasm and binuclear cells frequency in Chinese hamster V79 cells showed that AIR ( 2.9?.8 ii g/ml ) and d-TUB(27.5--55 i.i g/ml) increased the frequency of cells with abnormal nucleus/cytoplasm configuration cells as well as binuclear cells(P<0.00 1 ?.05);THH(O. I 56?.3 13mg/mi) increased the frequency of cells with abnormal cytokinesis (P<0.001),At high dose(0.3 13mg/mi) it also increased the frequency of binuclear cells 6 (P