OBJECTIVE: p53 gene is the most important human tumor suppressor gene. The purpose of this study was to explore the effect of p53 and its mutants on the transcriptional regulation of RhoE. METHODS：We constructed PEGFP-wt-p53 plasmid，and then synthesized p53 mutation hotspot plasmid (single point and double point mutations) by site-directed mutagenesis PCR technology. pGL3-RhoE-promotor-Luc plasmid transiently transfected the wild-type and mutant p53 plasmid into PC3 (p53-null) cells. Then the transcription activities of p53 and its mutants on RhoE were assessed by Dual-Luciferase reporter assay，and RhoE protein expression analyzed by western-blot. RESULTS：p53 protein could regulate the transcription activity of RhoE (P<0.05)，but the mutants lost this function. The effect of the different p53 mutants on RhoE transcription regulation showed no significant difference (P>0.05). The results was confirmed by western-blot on protein level. CONCLUSION：RhoE is one of the p53 regulated genes，but once p53 mutated，it would not able to regulate the transcription activity of RhoE anymore.

OBJECTIVE: To investigate the acute toxicity and genetic toxicity of tributyltin methoxide (TBTMO). METHODS: A total of 110 Kunming mice were randomly divided into 11 groups，then treated orally with various doses of TBTMO (420，286，194，180，132，90，73，61，41.5 and 28 mg/kg) to perform acute toxicity test. A total of 50 Kunming mice were randomly divided into 5 groups (TBTMO 80，40，20 mg/kg，positive control and negative control). Positive control was treated for five consecutive days. Other four groups were treated for two days. These animals were killed 35 d later，and their bilateral epididymis were removed for sperm shape abnormality test. Another 50 Kunming mice were randomly divided into 5 groups and treated as above mentioned. The animals were killed 30 h after gavage with TBTMO，and their chest bone marrow fluid were obtained for bone marrow micronucleus test. Another 50 GFP transgenic mice were randomly divided into 5 groups and treated as above. The animals were killed and their spleen lymphocyte was used for hprt gene mutation test. Various doses of TBTMO (69.4，48.6，34.0，23.8，16.6 and 0 μg/ml) were used to treat Chinese hamster lung (CHL) cell for chromosome aberration test. Different doses of TBTMO (5×105，5×104，5×103，5×102，50，5，0.5，0.05，5×10-3，5×10-4 μg/dish) were used to deal with TA97，TA98，TA100，TA102 strains for Ames test. RESULTS: The LD50 of TBTMO in mice was 98 mg/kg. TBTMO could induce sperm abnormality in a dose-dependent manner (P＜0.05). The other four tests showed negative results. CONCLUSION: Under our experimental conditions，TBTMO was classified as moderately-toxic substance. It may produce genetic toxicity.

OBJECTIVE: To provide the new insight into the quantitative health risk assessment on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in cigarette smoke. METHODS：Using the basic frame of health risk assessment and simulation and risk analysis，the probability distribution of exposure parameters were fitted，NNK incremental lifetime cancer risk(ILCR) was simulated by 2D simulation and 1D simulation. RESULTS：ILCR values，the calculated risks of NNK，were 6.66×10-4 and 1.29×10-4，and NNK should be highly controlled. And NNK release exerted a great influence on ILCR. CONCLUSION：We should be highly concerned about NNK and its carcinogenic risk.

OBJECTIVE: To investigate radiation-protective effect of piceatannol and acetylated resveratrol. METHODS：CCK-8 Assay Kit was used to detect the survival rate of AHH-1 cells treated by 0，10，20，50，100 and 500 μmol/L piceatannol or acetylated resveratrol for 72 h，or by 4 Gy γ-ray for 48 h after treatment with 0，10，20 and 50 μmol/L piceatannol or acetylated resveratrol for 2 h. Kunming mice were treated with resveratrol，piceatannol and acetylated resveratrol before 60Co γ-irradiation. The average life span and the WBC count post-irradiation were observed. RESULTS：Compared to control cells (0 μmol/L)，the survival rate of AHH-1 cells treated by 10，20 and 50 μmol/L piceatannol or acetylated resveratrol for 72 h was not changed (P>0.05)，but the survival rate of post-irradiation AHH-1 cells treated by 10，20 and 50 μmol/L piceatannol or acetylated resveratrol increased (P<0.05 or P<0.01). After radiation for 24 h，the WBC count of middle-dose (100 mg/kg) and high-dose(200 mg/kg) acetylated resveratrol groups increased (P<0.05). Compared to control group (0 μmol/L)，the average life span and the WBC count of radiation group decreased (P<0.05). Compared to radiation group，the average life span of mice in high-dose resveratrol or acetylated resveratrol groups increased. CONCLUSION：Piceatannol and acetylated resveratrol both had radiation-protective effect in post-radiation AHH-1 cells. In addition，acetylated resveratrol showed radiation-protective effect in post-radiation Kunming mice.

OBJECTIVE: To study the toxic oxidative damage in PC12 cells caused by microcystins-LR ( MC-LR). METHODS： MTT assays and lactate dehydrogenase (LDH) in culture medium of PC12 cells were performed to assess the toxicity of MC-LR. The contents of MDA，SOD，GSH-Px and CAT were measured with kits. RESULTS：MTT assay showed that MC-LR had an inhibitory effect on PC12 cells，and the IC50 of MC-LR were 89.06，47.24，33.13 μg/L at 12 h，24 h and 48 h，respectively. Twenty-four hours after treatment by MC-LR，the production of LDH in culture medium was increased. Compared with control group，the contents of MDA and SOD were apparent when MC-LR was more than 10 μg/L (P＜0.05). The catalase activity change was similar to SOD. GSH-Px content showed no significant difference compared with the control group. CONCLUSION： MC-LR could inhibit proliferation and induce membrane damage and oxidative damage in PC12 cells．

OBJECTIVE: To observe the toxic effects of allisartan isoproxil (ALS-3) on maternal Sprague-Dawley(SD) rats during pregnancy，lactation period，the growth and development，and the reproduction of their offsprings. METHODS：ALS-3 was administered by intragastric method at a dose level of 0 (control)， 30，90 or 270 mg/kg from day 15 of gestation to day 21 after parturition to examine the effects of ALS-3 on the reproductive capacity in the maternal rats and the growth and development of the offsprings. RESULTS： A pregnant rat (270 mg/kg) died due to dystocia. No obvious abnormality was observed in other maternal rats (F0) sacrificed 21 days after delivery. The body weight of F1 offspring on PND 7 and PND 21 in the 270 mg/kg group decreased significantly compared with control group (P<0.05)，and the body weight of F1 offsprings at other age and F2 offsprings in every test group showed no significant difference with control group (P>0.05). Compared with control group，the breast feeding mortality of F1 offsprings in the 270 mg/kg group was significantly increased，while F2 offsprings in the 90 mg/kg group decreased (P<0.01). Other indexes showed no significant difference compared with control group (P>0.05). CONCLUSION： ALS-3 at 270 mg/kg had obvious toxic effects on lactation of F0 generation and growth or development of F1 offsprings before weaning. However no effects on the functional，behavioral or learning abilities or reproductive performance in offsprings were observed in the 30 and 90 mg/kg groups.

OBJECTIVE: The study was performed to evaluate change of reproductive hormone level during early pregnancy in cynomolgus monkeys，and to collect background data to support the cynomolgus monkey embryo-fetal developmental toxicity evaluation model. METHODS：Blood samples from cynomolgus monkeys on gestation day 0(GD0) and gestation day 20(GD20) were collected to measure serum progesterone levels. Blood samples from pregnant monkeys were collected once a week during GD27-100 to measure serum estradiol，progesterone and prolactin levels by chemiluminescence method. RESULTS：Progesterone levels of pregnant female monkeys on GD20 were significantly higher than GD0. Progesterone level rose slowly from GD0 to GD27 until a peak，decreased to the trough on GD48，and then gradually rose until GD100. Estradiol level increased slowly from GD0 to GD27 until a peak，decreased to the lowest level on GD34，and then gradually rose until GD100. Prolactin level began to rise slowly from GD0 to GD69，and remained stable. CONCLUSION：Reproductive hormone levels in cynomolgus monkeys changed dynamically during early pregnancy. Progesterone levels can be used as supportive evidenced of early pregnancy.

OBJECTIVE: To investigate the genetic toxicity of bio-degradable polyglycolic acid (PGA) fiber materials and to assess its safety. METHODS：The bacterial reverse mutation study (Ames test) and the mouse lymphoma assay ( MLA) were used to test the potential genotoxicity. RESULTS： In Ames test，the bio-degradable PGA fiber material extract did not increase the revertant colonies (P＞0.5). From the mouse lymphoma assay，there was no significant difference of the clone forming rate between the PGA fiber extract group and the negative control group (P＞0.5)，however there was a significant difference between the PGA group and positive control group(P＜0.05). CONCLUSION：The bio-degradable PGA fiber material was not mutagenic as tested by Ames and mouse lymphoma assay.

OBJECTIVE: To study the determination and evaluation of intragastric administration of alcohol on antioxidative stress of rats. METHODS：The rats were gavaged with 50% alcohol (7.6 ml /kg) to establish the alcohol acute damage model，and then to measure the malondialdehyde (MDA) content，total antioxidant force(T-AOC)ability and superoxide dismutase (T-SOD) and catalase (CAT) activities in blood. RESULTS：The serum MDA content of experimental group was significantly higher than that in the control group (P<0.05). T-SOD was not significantly changed in either group. The aciticities of antioxidation enzyme such as CAT，GPx and GST in the experimental group were higher compared with negative control (P<0.05). T-AOC stayed the same. CONCLUSION：Oxidative stress could happen in over-drinking with more LPO production. At the same time the activities of antioxidative eyzmes were increased. The organism could keep the balance if the mechanism of oxidation-reduction remains intact.

OBJECTIVE: To evaluate the safety of flurbiprofen axetil 1ipid microspheres given as injection. METHODS：Acute toxicological test was conducted in dogs. Four dogs were given the tested drug at doses of 96，216，324 and 486 mg/kg intravenously and observed for 14 days. RESULTS：All animals suffered from various degrees of upper gastrointestinal bleeding. The animals given the dose of 96 and 216 mg/kg survived but the others died. CONCLUSION： The acute toxicity test showed that the approximate lethal dose of flurbiprofen axetil 1ipid microspheres for injection was 216-324 mg/kg in dogs.

OBJECTIVE: To analyze the pediatric tumor status，type and characteristics in Three Gorges Reservoir Region District，and to explore the control measures，so as to provide scientific basis for prevention. METHODS：From 2006 to 2009 there were 160 children with tumor found among 5 462 disabled children in 17 counties of Three Gorges Reservoir area. They were subject to statistical analysis. RESULTS：Thirty-seven different types of tumors were discovered in the 160 cases，including 13 types of benign tumors with 65 cases accounting for 40.62%，24 types of malignant tumor with 95 cases accounting for 59.38%. The top three tumors were 48 cases of hematological origin，41 of the nervous system and 23 of skin origin. The three most common malignant tumors were leukemia (hematological system) 40 cases (25%)， intracranial malignant tumor (nervous system) 33 cases (20.62%) and urogenital tumors 8 cases (5.0%). CONCLUSION：The common types of the children tumor in Three Gorges Reservoir Area mainly were acute and chronic lymphocytic leukemia and malignant intracranial tumors. To carry out early prevention of pediatric malignancy，early diagnosis and correct active treatment is the key to cure some malignant tumors，improve the survival rate and quality of life.

OBJECTIVE: To investigate the expression of TGF-β1 in congenital cystic adenomatoid malformation of the lung (CCAM) and its role in the formation of CCAM. METHODS： The diseased group included 52 cases of congenital cystoadenomatoid malformation of lung (6 m-15 y)，9 cases of normal lungs (2 m-15 y)and 15 fetal lungs at varying gestational ages (12-39 w) as the control group. Immunohistochemical staining (EliVision) was used to detect the proteins of TGF-β1，hybridization in situ to detect the mRNA of TGF-β1 in every tissue of CCAM，normal pediatric lungs and fetal lungs. RESULTS： The protein of TGF-β1 was mainly expressed in celluar cytoplasm of pulmonary epithelial cells and mesenchymal cells. The expression of TGF-β1 mRNA located in cytoplasm of smooth muscle cells surrounding the bronchus and cysts. The expression level of TGF-β1 and TGF-β1 mRNA in CCAM groups were significantly higher than those in fetal and normal lungs (P<0.05 or P<0.01)，but not significantly different among the diseased groups (P>0.05). CONCLUSION：The overexpression of TGF-β1 may play an important role in the development of congenital cystic adenomatoid malformation，and would warrant our further investigation.

OBJECTIVE: To explore expression characteristics of serum tumor markers AFP，CEA， CA19-9 in patients with the gastrointestinal malignant tumors. METHODS：Expression levels of AFP，CEA，CA19-9 in serum of 126 patients with gastrointestinal cancers were analyzed by Roche automatic electrochemical luminescence， and the relationship of these markers with clinicopathological factors were studied. RESULTS：Serum CEA expression increased with the depth of tumor invasion，clinical stage，and distant metastasis，the difference was statistically significant (P<0.05). Serum CA19-9 expression levels increased significantly with clinical stage，and distant metastasis difference (P<0.05). Serum level of AFP expression was not significantly different between the various clinical pathological factors. CONCLUSION： Expression levels of serum CEA，CA19-9 were closely related to the clinical condition of patients with gastrointestinal cancers.

OBJECTIVE: To investigate the genotoxicity of Zeiss “All in One Advance”(ZAOA). METHODS: Original product fluid was used as tested in bacterial reverse mutation test (Ames test) and mouse lymphoma assay (MLA) with and without metabolic activation of S9. Ames test was performed by the plate incorporation method for its ability to induce reverse mutations in three treatment dosage groups: 50，100，200 μl/plate using S．typhimurium TA98，TA100，TA1535，TA1537 and E．coli WP2 uvrA. Micropore method was employed in MLA，the mutation frequency (MF) and the percentage of small colony mutants of L5178 tk+/- cells induced by ZAOA at final concentration of 2.5%，5% and 10% (V/V) were calculated and assayed with +S9/3 h，-S9/3 h，-S9/24 h. Three concentrations of ZAOA of 0.5%，1%，2% were added for -S9/24 h. RESULTS: Ames test showed that ZAOA did not cause obvious increases in the mean number of revertant per plate in groups compared with negative control. MLA indicated that under the condition of -S9/24 h treatment，MF of 2.5% group was far above positive decision value，the relative total growth rate (RTG) was 3%. MF of 2% group，which RTG was up to 16%，did not reach positive decision value (P<0.01). CONCLUSION: ZAOA did not induce point mutation at his-/trp- to test strains. The frequency of gene tk+/- mutation increased significantly under the condition of -S9/24 h treatment，whether this could be related to its cytotoxic is still unknown.

OBJECTIVE: To study the acute toxicity and mutagenicity of aqueous extract of masson pine powder teabags. METHODS：Acute toxicity tests were done in mice and rats. Ames test，micronucleus test and sperm abnormality test were used to examine the acute toxicity and mutagenicity of aqueous extract of masson pine powder teabags. RESULTS：The of aqueous extract of masson pine needle powder teabags in mice and rats were both more than 240.0 g/kg. No statistical difference in revertant colonies was found in the Ames test with and without S9. The micronucleus rates and sperm abnormality rates in all doses showed no significant difference from the negative control. CONCLUSION：Aqueous extract of masson pine needle powder teabags showed no acute toxicity and mutagenicity under these test conditions.

OBJECTIVE: To study the embryo toxicity and teratogenecity of Chrysanthemum indicum extract in SD rats. METHODS：SD rats successfully impregnated were divided into 4 groups (15-16 animals per group)，included three Chrysanthemum indicum extract dosage groups (0.68，2.03，6.09 g/kg) and one negative control group. During gestation from 7-16 days，animals were orally gavaged with Chrysanthemum indicum ectract once daily，clinical manifestations and weight of the pregnant rats were collected during the study. On the 20th day pregnant rats were euthanized and the weight of placenta，body weight and length of fetus and the appearance，visceral and skeletal malformations of fetus were examined. RESULTS：No statistically significant difference was found in all the assessed indices(including the weight gain of pregnant rats，average live fetus，absorptive fetus ratio，body weight and length of fetus) between dosage and control groups (P＞0.05). CONCLUSION：Under our experimental conditions，chrysanthemum indicum extract showed no significant effects in the toxicity of SD pregnant rats，had no apparent teratogenicity and embryotoxicity.