AIM:To study the effect of arsenic trioxide (As_2O_3) on ratexperimental hepatocarcinoma and its renal cytotoxicity.METHODS:The hepatocarcinoma model was establishedby diethaylnitrosamine perfusion in stomach of 120 Wistarrats,and the treatment began at the end of 20 weeks.Before the treatment,the rat models were randomly dividedinto 5 groups.In the treatment groups,three doses ofAs_2O_3 were injected into rat abdominal cavity,the totaltime of drug administration was 4 weeks.Cisplatin controlor the blank group was injected into abdominal cavity withequal amount of cisplatin or saline at the same time,respectively.On the 7th,14th and 28th day after thetreatment,the hepatocarcinoma nodules were obtainedand the morphologic changes of hepatocarcinoma cellswere observed under light and electron microscopes;Immunohistochemistry (S-P methods) was employed todetect the expression of bcl-2,bax and PCNA inhepatocarcinoma tissues;flow cytometry (TUNEL assay)was used to detect the apoptosis of liver cancer cells andthe change of cytokinetics.On the 28th day,the kidneyswere obtained and their histologic changes were observedunder light microscope,and immunohistochemistry (SPstain) was a.lso employed to detect the expression of bcl-2and PCNA.Cisplatin and saline solution were used as thecontrol.RESULTS:As_2O_3 could induce the apoptosis of rat livercancer cells and exhibited typical morphologic changes.The incidence of apoptosis of hapatocarcinoma cells waselevated (P=0.001).The elevation was the most higher inthe group of middle-dose of As_2O_3 (1 mg·kg~(-1)),significantlyhigher than that of the other arsenic groups and the controls(P=0.001).Large dose of As_2O_3 (5 mg·kg~(-1)) was able toarise the incidence of apoptosis,but also produced a largeamount of necrosis and inflammatory reaction.Middle doseof As_2O_3 dramatically increased the cell number in G2/Mphase (P=0.0001),and apoptosis happened apparently.The expression of bcl-2 and bax was related to the dose ofAs_2O_3.With the up-regulation of apoptotic incidence,theratio of bcl-2/bak decreased.But the incidence of apoptosiswas not the highest status and the ratio of bcl-2/bax wasat the lowest when the highest-dose of As_2O_3 was used.There was significant difference among the PCNA indexes(PCNA L1) of the five groups.Of them,three arsenic groupsall showed decrease of different degrees,and this down- regulation was most obvious in group A.There wassignificant difference among the three groups (P=0.016).Under the light microscope,the rat kidney in the cisplatingroup exhibited tubular epithelium swelling anddegeneration,protein casts in collecting tubules;While allarsenic groups didn’t show the significant changes (P=0.013).In the arsenic groups,the expression of bcl-2 in the renaltubular epithelium was increased (P=0.005),no obviouschanges happened to PCNA L1.But in the group of cisplatin,the PCNA L1 increased significantly (P=0.001).CONCLUSION:As_2O_3 can induce apoptosis of rathepatocellular carcinoma cells.And there is optimum dose;too high dose will induce the cytotoxic effect,while certaindose of As_2O_3 is able to block the cell cycle at G2/M phase.As_2O_3 had the most remarkable influence on G2/M cells,and it can also induce apoptosis to cells at other phases.As_2O_3 can restrain the proliferation of rat hepatocellularcarcinoma cells,in a dose-time dependent manner.Compared with cisplatin,As_2O_3 didn’t show obvious renaltoxicity,which was related to the increasing expression ofbcl-2 in renal tubular epithelium,the inhibition of apoptosisand the anti-oxidation effects. AIM: To study the effect of arsenic trioxide (As 2 O 3) on rate of peripheral hepatocarcinoma and its renal cytotoxicity. METHODS: The hepatocarcinoma model was established by diethaylnitrosamine perfusion in stomach of 120 Wistarrats, and the treatment start at the end of 20 weeks. Before the treatment, the rat models were randomly divided into 5 groups.In the treatment groups, three doses ofAs_2O_3 were injected into rat abdominal cavity, the total time of drug administration was 4 weeks. Cathplatin controlor the blank group was injected into abdominal cavity withequal amount of cisplatin or saline at the same time, respectively. On the 7th, 14th and 28th day after the treatment, the hepatocarcinoma nodules were obtained and the morphologic changes of hepatocarcinoma cellswere observed under light and electron microscopes; Immunohistochemistry (SP methods) was employed todetect the expression of bcl-2, bax and PCNA in hepatocarcinoma tissues; flow cytometry (TUNEL assay) was used to detect the apoptosis of liv er cancer cells and the change of cytokinetics. On the 28th day, the kidneyswere obtained and their histologic changes were observedunderlight microscope, and immunohistochemistry (SPstain) was a. lso employed to detect the expression of bcl-2and PCNA.Cisplatin and saline solution were used as thecontrol.RESULTS: As_2O_3 could induce the apoptosis of rat liver cancer cells and cannons show typical morphologic changes. The incidence of apoptosis of hapatocarcinoma cells waselevated (P = 0.001). Elevation was the most higher inthe group of middle-dose of As_2O_3 ( 1 mg · kg -1, significantlyhigher than that of the other arsenic groups and the controls (P = 0.001) .Large dose of As 2 O 3 (5 mg · kg -1) was able toarize the incidence of apoptosis , but also produced a large mount of necrosis and inflammatory reaction. Middle dose of As_2O_3 increased increased the cell number in G2 / Mphase (P = 0.0001), and apoptosis happened apparently. The expression of bcl-2 and bax was related to the dose of As_2O_3. With the up-regulation of apoptotic incidence, the ratio of bcl-2 / bak decreased.But the incidence of apoptosis was not the highest status and the ratio of bcl-2 / bax wasat the lowest when the highest-dose of As_2O_3 was used. Significant differences among the PCNA indexes (PCNA L1) of the five groups. Of them, three arsenic groups were showed decrease of different degrees, and this down-regulation was most obvious in group A. Every WAssignificant difference among the three groups (P = 0.016 ) .Under the light microscope, the rat kidney in the cisplating group, tubular epithelium swelling and degeneration, protein casts in collecting tubules; While allarsenic groups did not show the significant changes (P = 0.013) .In the arsenic groups, the expression of bcl -2 in the renal tubular epithelium was increased (P = 0.005), no obvious change happened to PCNA L1.But in the group of cisplatin, the PCNA L1 increased significantly (P = 0.001) .CONCLUSION: As_2O_3 can induce apoptosis of rathepatocellular carcinoma cel ls.And there is optimum dose; too high dose will induce the cytotoxic effect, while certain of as_2O_3 is able to block the cell cycle at G2 / M phase. As_2O_3 had the most remarkable influence on G2 / M cells, and it can also induce apoptosis to cells at other phases. As_2O_3 can restrain the proliferation of rat hepatocellular carcinoma cells, in a dose-dependent dependent manner. Compared with cisplatin, As_2O_3 did not show obvious renal toxicity, which was related to the increasing expression of bcl-2 in renal tubular epithelium, the inhibition of apoptosis and the anti-oxidation effects.