Basic Investigations EXPRESSION OF GAP JUNCTION PROTEIN Cx43 IN CULTURED HUMAN NORMAL AND MALIGNANT LUNG CELLS

ＢａｓｉｃＩｎｖｅｓｔｉｇａｔｉｏｎｓＥＸＰＲＥＳＳＩＯＮＯＦＧＡＰＪＵＮＣＴＩＯＮＰＲＯＴＥＩＮＣｘ４３ＩＮＣＵＬＴＵＲＥＤＨＵＭＡＮＮＯＲＭＡＬＡＮＤＭＡＬＩＧＮＡＮＴＬＵＮＧＣＥＬＬＳＺｈａｎｇＺｈｉｑｉａｎ；张志谦；ＬｉｎＺｈｏｎｇｘｉａｎｇ...     

PROMOTION OF CHEMICAL CARCINOGENESIS AND P53 EXPRESSION BY REDUCTION OF SUPEROXIDE DISMUTASE ACTIVITY IN THE LUNG OF RAT IN V

ＰＲＯＭＯＴＩＯＮＯＦＣＨＥＭＩＣＡＬＣＡＲＣＩＮＯＧＥＮＥＳＩＳＡＮＤＰ５３ＥＸＰＲＥＳＳＩＯＮＢＹＲＥＤＵＣＴＩＯＮＯＦＳＵＰＥＲＯＸＩＤＥＤＩＳＭＵＴＡＳＥＡＣＴＩＶＩＴＹＩＮＴＨＥＬＵＮＧＯＦＲＡＴＩＮＶＩＶＯ￥ＹｕＬｕｎｙｉｎ；喻伦银；Ｂｉ...     

CLINICOPATHOLOGIC FEATURES AND DIAGNOSISOF COMBINED HEPATOCELLULAR ANDCHOLANGIOCARCINOMA

ＣＬＩＮＩＣＯＰＡＴＨＯＬＯＧＩＣＦＥＡＴＵＲＥＳＡＮＤＤＩＡＧＮＯＳＩＳＯＦＣＯＭＢＩＮＥＤＨＥＰＡＴＯＣＥＬＬＵＬＡＲＡＮＤＣＨＯＬＡＮＧＩＯＣＡＲＣＩＮＯＭＡＬｕＪｉａｎｐｉｎｇ路建平；ＣａｉＷｅｉｍｉｎ蔡为民；ＨａｙａｓｈｉＫｅｉｋｉ１林肇辉...     

CLONING AND SEQUENCING OF IMMUNOGLOBULINVARIABLE－REGION GENE OF A MONOCLONALANTIBODY SPECIFIC FOR HUMANHEPATOCARCINOMA

ＣＬＯＮＩＮＧＡＮＤＳＥＱＵＥＮＣＩＮＧＯＦＩＭＭＵＮＯＧＬＯＢＵＬＩＮＶＡＲＩＡＢＬＥ－ＲＥＧＩＯＮＧＥＮＥＯＦＡＭＯＮＯＣＬＯＮＡＬＡＮＴＩＢＯＤＹＳＰＥＣＩＦＩＣＦＯＲＨＵＭＡＮＨＥＰＡＴＯＣＡＲＣＩＮＯＭＡＹａｎｇＰｉｎｇ杨萍；ＧａｏＬｅｉ高...     

IMAGING FINDINGS OF MALIGNANT FIBROUS HISTOCYTOMA (MFH) IN THE LUNG

ＩＭＡＧＩＮＧＦＩＮＤＩＮＧＳＯＦＭＡＬＩＧＮＡＮＴＦＩＢＲＯＵＳＨＩＳＴＯＣＹＴＯＭＡ（ＭＦＨ）ＩＮＴＨＥＬＵＮＧＤａｉＪｉｎｇｒｕｉ戴景蕊ＪｉａｎｇＬｉｍｉｎｇ蒋力明ＺｈａｎｇＹｕ张宇ＺｈａｎｇＸｉａｏｂｏ张晓波ＣａｎｃｅｒＩｎｓｔｉｔｕｔｅ（Ｈ...     

COMBINED IL-2/IL-3 GENE THERAPY FOR G422 MOUSE GLIOBLASTOMA BY INTRATUMORAL INJECTION OF RECOMBINANT ADENOVIRUSES

ＣＯＭＢＩＮＥＤＩＬ２／ＩＬ３ＧＥＮＥＴＨＥＲＡＰＹＦＯＲＧ４２２ＭＯＵＳＥＧＬＩＯＢＬＡＳＴＯＭＡＢＹＩＮＴＲＡＴＵＭＯＲＡＬＩＮＪＥＣＴＩＯＮＯＦＲＥＣＯＭＢＩＮＡＮＴＡＤＥＮＯＶＩＲＵＳＥＳ１ＨｏｎｇＢｏ２洪波ＣａｏＸｕｅｔａｏ３曹雪涛Ｙｕ...     

EXPERIMENTAL STUDIES ON RADIATION-INDUCIBLE HUMAN TNF GENE THERAPY FOR CANCER

ＥＸＰＥＲＩＭＥＮＴＡＬＳＴＵＤＩＥＳＯＮＲＡＤＩＡＴＩＯＮ－ＩＮＤＵＣＩＢＬＥＨＵＭＡＮＴＮＦＧＥＮＥＴＨＥＲＡＰＹＦＯＲＣＡＮＣＥＲＣａｏＸｕｅｔａｏ曹雪涛ＺｈａｎｇＷｅｉｐｉｎｇ章卫平ＷａｎｇＪｉａｎｌｉ王建莉ＨｕａｎｇＸｉｎ黄欣ＱｉｎＺｈｉｈ...     

STUDIES ON THE GAP JUNCTIONAL INTERCELLULARCOMMUNICATION OF HUMAN NASOPHARYNGEALCARCINOMA CELLS AND THE EFFECT OF RII

ＳＴＵＤＩＥＳＯＮＴＨＥＧＡＰＪＵＮＣＴＩＯＮＡＬＩＮＴＥＲＣＥＬＬＵＬＡＲＣＯＭＭＵＮＩＣＡＴＩＯＮＯＦＨＵＭＡＮＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣＩＮＯＭＡ　ＣＥＬＬＳＡＮＤＴＨＥＥＦＦＥＣＴＯＦＲＩＩＨａｎＬｉｑｕｎ韩立群；ＧａｏＪｉｎ高进；...     

COMPARATIVE PATHOLOGICAL AND FCM STUDIES ON THE PRIMARY AND METASTATIC CANCERS IN STOMACH AND BREAST

ＣＯＭＰＡＲＡＴＩＶＥＰＡＴＨＯＬＯＧＩＣＡＬＡＮＤＦＣＭＳＴＵＤＩＥＳＯＮＴＨＥＰＲＩＭＡＲＹＡＮＤＭＥＴＡＳＴＡＴＩＣＣＡＮＣＥＲＳＩＮＳＴＯＭＡＣＨＡＮＤＢＲＥＡＳＴ￥ＺｈａｎｇＸｉａｎｇｈｏｎｇ；张祥宏；ＺｈａｎｇＪｉｅｙｉｎｇ；张杰英；Ｘｉ...     

ISOLATION AND CHARACTERIZATION OF AN ADRIAMYCIN－RESISTANT SUBLINE OF THE HUMAN GASTRIC ADENOCARCINOMA CELLLINE

ＩＳＯＬＡＴＩＯＮＡＮＤＣＨＡＲＡＣＴＥＲＩＺＡＴＩＯＮＯＦＡＮＡＤＲＩＡＭＹＣＩＮ－ＲＥＳＩＳＴＡＮＴＳＵＢＬＩＮＥＯＦＴＨＥＨＵＭＡＮＧＡＳＴＲＩＣＡＤＥＮＯＣＡＲＣＩＮＯＭＡＣＥＬＬＬＩＮＥＷａｎｇＹａｎｐｉｎｇ；王艳萍；ＸｕＧａｎｇ；徐刚（Ｉ...     

The blocking effects of glycyrrhize uralensis and chelidonium majus on mutagenesis induced by Aflatoxin Bl

Glycyrrhiza Uralensis (GU) and Chelidonium Majus (CM) (25, 50, 100, 200 mg/plate) have obvious blocking effects onSalmonella Typhimurium strains (TA97, TA98, TA100, TA102) mutagenesis induced by aflatoxin Bl (AFB1). The blocking rates of GU and CM are more dependent on the doses. A compound of GU and CM, called Wei Lingsu (WLS), could impede chromosomol aberrations and sister chromatid exchanges (SCE) of human peripheral lymphocyte induced by AFB1, at the concentrations of 1–50 mg/ml, the blocking rates are 52.94%–88.24% and 15. 50%–38.23% saperatly. WLS could also impede the inhibition of AFB1 to lymphocyte mitosis.     

甲氨基阿维菌素的致突变性、致畸性及亚慢性毒性的研究

目的与方法:本文报道了甲氨基阿维菌素小鼠骨髓嗜多染红细胞微核试验,小鼠精子畸形试验,Ames 试验,对大鼠的亚慢性毒性试验及致畸试验的研究结果。结果与结论:其剂量在6. 3～25. 2mg/ kg 的微核试验结果表明,各剂量组与阴性对照组的微核率比较,结果无显著意义( P > 0105) 。10～500μg/ 皿剂量组Ames 试验及15. 8～63mg/ kg. bw 剂量组小鼠精子畸形试验结果均为阴性。致畸研究结果表明,该药对大鼠无明显母体毒作用和胚胎毒作用。亚慢性毒性试验中,高剂量组雌性大鼠(9. 26mg/ kg. bw) 尿素氮、雄性大鼠(12. 6mg/ kg. bw) 尿素氮及白蛋白水平有一定程度的改变,雄、雌性大鼠肾脏脏器系数有显著的改变( P < 0105) 。雄性大鼠(12. 6mg/ kg. bw) 体重明显降低( P < 0105) ,比雌性大鼠影响略大。亚慢性毒性最大耐受剂量雌性大鼠为1. 16mg/ kg. bw ,雄性大鼠为1. 57mg/ kg. bw。     

萝卜硫素对免疫抑制小鼠的免疫调节作用

目的 探讨萝卜硫素对免疫抑制小鼠免疫功能的保护作用。方法 实验用小鼠随机分为4组：对照组、环磷酰胺（Cy）模型组、萝卜硫素高剂量组（30 mg/kg）和萝卜硫素低剂量组（15 mg/kg）,灌胃给药,比较四组小鼠脾脏指数、胸腺指数、腹腔巨噬细胞吞噬功能、血清溶血素含量以及外周血淋巴细胞转化率;运用RT-PCR半定量法观察免疫调节基因TGF-β和PD-1mRNA的表达。结果 与对照组相比,免疫抑制小鼠血清溶血素OD值（0.702±0.08）、外周血淋巴细胞的转化率（42.22%）、胸腺指数（1.25±0.21）和脾脏指数（2.73±0.26）、吞噬百分率（31.86%）和吞噬指数（0.73±0.06）显著下降（P＜0.05）;但是与环磷酰胺模型组比较,萝卜硫素组小鼠血清溶血素OD值（1.325±0.10）、外周血淋巴细胞的转化率（51.44%）、胸腺指数（1.89±0.31）和脾脏指数（3.80±0.46）、吞噬百分率（43.56%）和吞噬指数（1.15±0.08）明显增加（P＜0.05）,免疫调节基因TGF-β和PD-1mRNA的表达量下降,并且具有剂量依赖性。结论 萝卜硫素可明显改善环磷酰胺免疫抑制小鼠的免疫功能,同时能有效抑制免疫调节基因TGF-β和PD-1的过度表达。     

Comparative aflatoxin B1 mutagenesis of Salmonella typhimurium TA 100 in metabolic and photoactivation systems

Salmonella typhimurium TA 100 was mutagenized with photoactivated aflatoxin B1 (AFB1) and AFB2. Levels of mutagenesis induced by AFB1 correlated with levels of in vitro covalent binding of [3H]AFB1 to calf thymus DNA. The same phenomenon was observed with AFB2. Photoactivated AFB1 induced lethality in the mutagenized cultures, and AFB2 failed to do so. Extraction of nucleic acids from cultures mutagenized by photoactivated or metabolically activated [3H]AFB1 revealed that: (a) in situ levels of [3H]AFB1 binding to DNA were proportional to induction of mutational and lethal events in both cases; (b) mammalian metabolism and photoactivation produced AFB1:DNA lesions possessing comparable lethality and mutagenicity; and (c) [3H]AFB1 binding levels to bacterial RNA did not correlate with mutagenesis and lethality.     

Preliminary study on the antimutagenesis of vegetables and fruits

Possible antimutation of 108 preparations of 91 kinds of vegetables and fruits on Salmonella typhimurium TA98 and TA100 mutants was tested. 4-nitroquinoline-N-oxide (4 NQO), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), aflatoxin B1 (AFB1) and benzo (a) pyrene (BaP) were used as mutagens. The results showed that 67 (62%) preparations had antimutagenic action in vitro to different degrees. 9.6% of all preparations showed inhibition action on 4 NQO in TA100 mutant and 12.3%, in TA98, 5% on MNNG in TA100, 38% on AFB1 in TA100 and 45.1% in TA98, 28.9% on BaP in TA100. This experiment provides a scientific basis to the study of food resources as prevention of carcinogenesis.     

黄芪总苷诱导人白血病NB4细胞凋亡的机制

目的 研究黄芪总苷(TA)对体外培养的人早幼粒细胞白血病细胞株NB4增殖及凋亡机制的影响.方法 将不同浓度的TA与NB4细胞共培养48 h,采用细胞增殖及细胞毒性检测试剂盒8(CCK-8)检测细胞生长抑制率,以流式细胞仪检测细胞凋亡率及凋亡过程中细胞内核因子κB(NF-κB)和蛋白激酶B(PKB,又称Akt)蛋白浓度的变化.结果 200、400、600、800 ms/L TA均可抑制NB4细胞生长,抑制率分别为(14.54±3.20)%、(24.79±3.98)%、(57.28±4.71)%和(88.28±4.65)%,呈浓度依赖性增加(P<0.05).200、400、600、800 mg/L TA组的细胞凋亡率分别为(10.03±3.31)%、(14.87±3.65)%、(23.45±1.90)%和(25.26 4-2.07)%,与对照组[(1.80±1.24)%]相比,差异均有统计学意义(P<0.05),且200、400、600 ms/L TA组的细胞凋亡率呈浓度依赖性增加(P<0.05);800 mg/L TA组的细胞凋亡率增加不明显,与600 ms/L TA组相比,差异无统计学意义(P>0.05),但出现了大量的坏死细胞,坏死率达(45.65±3.16)%.细胞凋亡过程中伴随NF-κB蛋白表达下降,不同浓度TA组与对照组差异均有统计学意义(P<0.05),而Akt蛋白的表达无明显变化(P>0.05).结论 黄芪总苷可以抑制NB4细胞增殖,并可以通过不依赖Akt的NF-κB信号通路来诱导NB4细胞凋亡.

Abstract：

Objective To investigate the effect of total astragalosides (TA) on proliferation and apoptosis in human leukemia NB4 cells in vitro. Methods The NB4 cells were treated with TA at different concentrations for 48 h in culture. Growth inhibition rates were measured by CCK-8 method. Flow cytometry was used to explore the cell apoptosis and the activity of NF-κB and Akt during apoptosis. Results TA at different concentrations (200, 400, 600, 800 mg/L) inhibited proliferation of NB4 cells in a dose-dependent manner ( P < 0. 05), and the inhibitory rates of TA on NB4 cells were (14. 54 ± 3. 20) % , (24.79 ±3.98)%, (57.28 ±4.71)% and (88.28 ±4.65)% , respectively. In terms of the induction of apoptosis, there was a significant difference between the TA group and blank control [(1.80±1.24)%, P<0.05]. At TA doses of 200, 400 and 600 mg/L, the apoptotic rates of NB4 cells were ( 10. 03 ± 3.31)% , (14.87 ±3.65)% , (23.45 ± 1.90) % , respectively. Besides, TA induced apoptosis of NB4 cells in a dose-dependent manner in the groups of 200 mg/L, 400 mg/L, 600 mg/L (P<0.05). But there was no significant difference in apoptotic rates between the groups of 800 mg/L and 600 mg/L [(23.45 ±1.90)%, P> 0.05]. In the group of 800 mg/L, the necrotic cells increased highly and the necrotic rate reached (45.65 ± 3.16)%. After TA treatment of NB4 cells at different concentrations (200, 400, 600 mg/L), the expression of NF-kB protein was significantly decreased compared with that of the blank control (9. 79 ±0. 95, P<0.05), while Akt protein was not significantly decreased (P>0.05). Conclusion TA can inhibit the growth of NB4 cells and induce apoptosis in NB4 cells through an Akt-independent NF-kB signaling pathway.     

Grapefruit juice intake does not enhance but rather protects against aflatoxin B1-induced liver DNA damage through a reduction in hepatic CYP3A activity

Influence of grapefruit juice intake on aflatoxin B1 (AFB1)-induced liver DNA damage was examined using a Comet assay in F344 rats given 5 mg/kg AFB1 by gavage. Rats allowed free access to grapefruit juice for 5 days prior to AFB1 administration resulted in clearly reduced DNA damage in liver, to 65% of the level in rats that did not receive grapefruit juice. Furthermore, rats treated with grapefruit juice extract (100 mg/kg per os) for 5 days prior to AFB1 treatment also reduced the DNA damage to 74% of the level in rats that did not receive grapefruit juice. No significant differences in the portal blood and liver concentrations of AFB1 were observed between grapefruit juice intake rats and the controls. In an Ames assay with AFB1 using Salmonella typhimurium TA98, lower numbers of revertant colonies were detected with hepatic microsomes prepared from rats administered grapefruit juice, compared with those from control rats. Microsomal testosterone 6beta-hydroxylation was also lower with rats given grapefruit juice than with control rats. Immunoblot analyses showed a significant decrease in hepatic CYP3A content, but not CYP1A and CYP2C content, in microsomes of grapefruit juice-treated rats than in non-treated rats. No significant difference in hepatic glutathione S-transferase (GST) activity and glutathione content was observed in the two groups. GSTA5 protein was not detected in hepatic cytosol of the two groups. In microsomal systems, grapefruit juice extract inhibited AFB1-induced mutagenesis in the presence of a microsomal activation system from livers of humans as well as rats. These results suggest that grapefruit juice intake suppresses AFB1-induced liver DNA damage through inactivation of the metabolic activation potency for AFB1 in rat liver.     

Effect of allixin, a phytoalexin produced by garlic, on mutagenesis, DNA-binding and metabolism of aflatoxin B1

Allixin, a phytoalexin isolated from garlic, was examined for its effects on aflatoxin B1(AFB1)-induced mutagenesis using Salmonella typhimurium TA100 as the bacterial tester strain and rat liver S9 fraction as the metabolic activation system. The effects of allixin on the binding of [3H]AFB1 to calf thymus DNA and on the formation of metabolites of [3H]AFB1 were also determined. Allixin showed a dose-related inhibition of Histidine+ revertants induced by AFB1. Allixin at 75 micrograms/ml inhibited [3H]AFB1 binding to calf thymus DNA and reduced formation of AFB1-DNA adducts. In addition, allixin exhibited a concentration-dependent inhibition of the formation of organosoluble metabolites and the glutathione conjugates of [3H]AFB1. The data indicate that the effect of allixin on AFB1-induced mutagenesis and binding of metabolites to DNA may be mediated through an inhibition of microsomal P-450 enzymes. Allixin may thus be useful in the chemoprevention of cancer.     

The effects of cyclophosphamide on in vitro correlates of tumor immunity

The effects of cyclophosphamide (CY) on tumor immunity against isografts of rat sarcomas induced by polyoma virus were studied using in vitro techniques. Groups of sarcoma-bearing animals received CY (250 mg/kg intraperitoneally 11 days after isografting) CY (150 mg/kg IP 8 days after isografting), or IP injections of 0.9% NaCl. In control rats tumor growth was progressive. All CY-treated animals showed transient tumor regression of at least 50% of their pretreatment tumor volume. Despite a drastic depression in numbers of blood leukocytes as well as lymph-node cells following CY treatment, animals treated with 150 mg/kg CY were shown to have blood lymphocyte and lymph-node cell cytotoxicity in vitro against plated sarcoma target cells comparable to untreated sarcoma-bearing animals. Sera obtained from sracoma-bearing rats prior to CY treatment specifically blocked lymphocyte cytotoxicity against sarcoma target cells. After CY treatment serum blocking activity could not be demonstrated during the period of tumor regression, but reappeared in parallel with tumor regrowth. Antibodies cytotoxic to sarcoma target cells when homologous complement was added could not be demonstrated in sera obtained from animals before CY treatment, but were present after treatment during tumor remission. Following CY treatment, sera obtained from treated animals, when mixed with blocking sera from control animals, could counteract or unblock the blocking activity of tumor-bearer sera. Unblocking capacity was present only in sera obtained during CY-induced tumor remission. Serum IgG concentration was significantly and temporarily decreased after CY treatment.     

Enhancing effect of ethanol on aflatoxin B1-induced hepatocarcinogenesis in male ACI/N rats

The modifying effect of ethanol (EtOH) on aflatoxin B1 (AFB1)-induced hepatocarcinogenesis was examined in male ACI/N rats by chronic treatment at the post-initiation phase. Rats received an ip injection of AFB1 (1.5 mg/kg) twice a week for 10 weeks (a total of 20 doses). Following a week of acclimation, they were given 10% EtOH as drinking water for 56 weeks. The effect of EtOH on the hepatocarcinogenesis was evaluated in terms of the incidence of altered hepatocellular foci and neoplasms at the end of the experiment. Exposure to AFB1 alone induced a substantial number of altered foci (6.98 iron-excluding foci/cm2) in rats. The number of altered liver cell foci in rats receiving AFB1 followed by EtOH was significantly increased (26.39 iron-excluding foci/cm2). In the rats given EtOH after AFB1, the total area and mean diameter of both iron-excluding foci and altered foci identified in hematoxylin and eosin-stained sections were significantly higher than in the rats exposed to AFB1 alone. The incidence of liver cell tumors of the group given AFB1 and EtOH (3/15, 20%) was higher than that of the group treated with AFB1 alone (0/14, 0%). Treatment with EtOH alone for 56 weeks did not induce either. These results indicate an enhancing effect of EtOH on AFB1-induced hepatocarcinogenesis when it is given in the promotion phase.