Benzo(a)pyrene-induced genotoxicity: Attenuation by farnesol in a mouse model

In the present study we have evaluated the antigenotoxic effects of Farnesol (FL) a 15-carbon isoprenoid alcohol against benzo (a) pyrene [B(a)P] (125 mg kg^{? 1}.b.wt oral) induced toxicity. B(a)P administration lead to significant induction in Cytochrome P450 (CYP) content and aryl hydrocarbon hydrolase (AHH) activity (p < 0.001), DNA strand breaks and DNA adducts (p < 0.001) formation. FL was shown to suppress the activities of both CYP and AHH (p < 0.005) in modulator groups. FL pretreatment significantly (p < 0.001) restored depleted levels of reduced glutathione (GSH), quinone reductase (QR) and glutathione –S-transferase (GST). A simultaneous significant and at both the doses reduction was seen in DNA strand breaks and in in-vivo DNA adducts formation (p < 0.005), which gives some insight on restoration of DNA integrity. The results support the protective nature of FL. Hence present data supports FL as a future drug to preclude B (a) P induced toxicity.     

Immunomodulation of carcinogens-induced steroids-dependent human diseases

The experimental and clinical data about antibodies against environmental chemical carcinogens and endogenous steroids are represented. The conception of immunomodulation of carcinogens- and steroids-dependent human diseases is proposed. It is postulated that antibodies to polycyclic aromatic hydrocarbons and heterocyclic amines in cooperation with antibodies to cholesterol, sex hormones, mineralo- and glucocorticoids stimulate or inhibit cancer, malformation, cardiovascular and autoimmune diseases depending on their personal combination. It is recommended to use immunoassay of these antibodies for the human diseases prediction. The alternative approaches for prevention using the probiotics transformed by anti-carcinogen antibodies are substantiated.     

有机污染物芘胁迫下白菜生理特性变化规律

为探究多环芳烃芘对白菜生理特性的影响,通过盆栽实验对华北地区常见的11种白菜进行不同浓度芘胁迫下的培养,研究白菜生理指标的变化规律。结果表明：白菜的种类和芘的浓度对白菜生理指标（生物量、丙二醛、叶绿素）均有显著影响,且随芘浓度变化,不同种类白菜的生理指标呈现不同的变化规律。白菜的生物量随芘的添加呈现两种变化：一是随芘添加浓度增加白菜生物量逐渐下降;二是在中低浓度芘（5、15、45 mg/kg）处理白菜生物量升高,高浓度（135、405 mg/kg）胁迫下生物量下降。白菜的丙二醛（MDA）含量随芘浓度的增加,表现出3种不同规律：各浓度之间均无显著性差异,MDA含量逐渐升高,以及显著低于对照组。叶绿素含量随芘浓度的增加,主要呈现出先下降后上升和逐渐上升2种变化趋势。京春白（JCB）和中白50（ZB-50）对芘的胁迫具有良好的耐受性,生理指标变化较小;中浓度芘胁迫下京翠60（JC-60）和京春绿（JCL）较为敏感,高浓度下京秋65（JQ-65）和吉红308（JH-308）生理指标变化显著,可以作为中低浓度和高浓度芘污染土壤指示作物。     

N′-Isopropylnornicotine in Burley Tobacco (Nicotiana tabacum)

Allyl sulfides such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), typical flavor components of Allium vegetables, have been shown to inhibit benzo[a]pyrene (B[a]P)-induced carcinogenesis in animal models. As a possible mechanism of this inhibition, the effect of these volatile substances on cytochrome P450 (CYP)1 (CYP1A1, 1A2 and 1B1)-mediated bioactivation of B[a]P was investigated using a human hepatoma cell model (HepG2). DADS and DATS inhibited the B[a]P-induced ethoxyresorufin O-deethylase (EROD) activity, a marker enzyme for CYP1, by 30-90% and 70-95% at 100-1,000 μM concentration, respectively. The cell viability, an indicator of the capacity to inhibit B[a]P bioactivation, was increased by treatments of 100-1,000 μM DADS and 10-100 μM DATS. Immunoblot results indicated that the B[a]P inducible CYP1A2 protein was suppressed by 100-1,000 μM of DADS and 10-100 μM of DATS, but CYP1A1 and 1B1 were not detectable in any microsomes. Analysis of B[a]P metabolites revealed that the level of 7,8-diol formed was significantly reduced in the DADS and DATS treated microsomes as compared to the control. The level of 9,10-diol and 4,5-diol formed was also lowered by the allyl sulfide treatments. These results suggest that the protective mechanism of allyl sulfides on B[a]P-induced carcinogenesis is possibly related with the modulation of CYP1-mediated bioactivation of B[a]P.     

3，4苯并芘对内皮祖细胞生物学功能的影响

目的研究3,4苯并芘（BaP）对人脐血来源的内皮祖细胞（EPC）生物学功能的影响。方法密度梯度离心法分离获取人脐血单个核细胞,采用贴壁培养法培养MNC中的EPC,通过Dil标记的乙酰化低密度脂蛋白（Dil-ac-LDL）摄取实验和FITC标记的植物凝集素（FITC-UEA-I lectin）结合实验鉴定细胞。消化收集第3代细胞,分别采用细胞计数试剂盒（CCK-8）、黏附能力测定实验、Transwell小室法及Matrigel体外成血管试验观察BaP对EPC增殖能力、粘附能力、迁移能力及成血管能力的影响,并检测各组细胞培养上清液SOD含量。采用单因素方差分析及LSD-t检验进行统计学分析。结果采用贴壁培养法能成功培养出EPC;与正常对照组相比,BaP呈浓度依赖性降低EPC的增殖能力{正常对照组OD（1.02±0.04）显著高于BaP各组[BaP①组OD（0.66±0.04）,BaP②组OD（0.55±0.04）,BaP③组OD（0.35±0.05）,均P〈0.01],BaP染毒组间增殖能力差异亦有统计学意义（两两比较,均P〈0.01）};与正常对照组比较,BaP呈浓度依赖性降低EPC的黏附能力{正常对照组[（117.50±17.16）个/200倍镜]显著高于BaP各组[BaP①组（80.00±14.46）个/200倍镜,BaP②组（66.00±9.06）个/200倍镜,BaP③组（49.80±10.72）个/200倍镜,均P〈0.01],BaP染毒组间黏附能力差异亦有统计学意义（两两比较,均P〈0.05）};与正常对照组相比,EPC的迁移能力亦呈BaP浓度依赖性降低{正常对照组[（46.10±4.51）个/400倍镜]显著高于BaP各组[BaP①组（35.50±4.95）个/400倍镜,BaP②组（26.80±4.08）个/400倍镜,BaP③组（19.50±2.84）个/400倍镜,均P〈0.01],BaP染毒组间迁移能力差异亦有统计学意义（两两比较,均P〈0.01）};与正常对照组比较,EPC的成血管能力亦呈BaP浓度依赖性降低{正常对照组[（33.20±3.70）个/100倍镜]显著高于BaP各组[BaP①组（22.00±3.39）个/100倍镜,BaP②组（16.20±2.59）个/100倍镜,BaP③组（10.80±2.39）个/100倍镜,均P〈0.01],BaP染毒组间成血管能力差异亦有统计学意义（两两比较,均P〈0.05）}。同时细胞培养上清液中SOD的活力也呈BaP浓度依赖性地降低{正常对照组[（22.6±2.19）U/ml]高于BaP各组[BaP①组（15.94±1.68）U/ml,BaP②组（12.5±1.58）U/ml,BaP③组（6.9±1.55）U/ml,均P〈0.01],BaP染毒组间SOD活力差异亦有统计学意义（两两比较,均P〈0.01）}。结论 BaP体外诱导显著影响EPC的多种生物学功能,其机制可能与氧化损伤有关。     

Dual character of Toll-like receptor signaling: Pro-tumorigenic effects and anti-tumor functions

As a major class of pattern-recognition receptors, Toll-like receptors (TLRs) play a critical role in defense against invading pathogens. Increasing evidence demonstrates that, in addition to infection, TLRs are involved in other important pathological processes, such as tumorigenesis. Activation of TLRs results in opposing outcomes, pro-tumorigenic effects and anti-tumor functions. TLR signaling can inhibit apoptosis and promote chronic inflammation-induced tumorigenesis. TLR activation in tumor cells and immune cells can induce production of cytokines, increase tumor cell proliferation and apoptosis resistance, promote invasion and metastasis, and inhibit immune cell activity resulting in tumor immune escape. In contrast, the engagement of other TLRs directly induces growth inhibition and apoptosis of tumor cells and triggers activation of immune cells enhancing anti-tumor immune responses. Thus, the interpretation of the precise function of each TLR in tumors is very important for targeting TLRs and using TLR agonists in tumor therapy. We review the role of TLR signaling in tumors and discuss the factors that affect outcomes of TLR activation.     

Optimized cultivation of highly-efficient degradation bacterial strains and their degradation ability towards pyrene

Two bacterial strains,Pyl and Py4,have been tamed and isolated through long cultivation with polycyclic aromatic hydrocarbon-pyrene as the single carbon source.It has been proven that they are both highly-efficient pyrene degrading bacteria and both Bacillus sp..The pyrene degradation ability of separated Pyl,Py4 and the consortium of equal Pyl and Py4 was studied in this project.It is shown that pyrene degradation rates were 88% in 10hr by Py1,84% in 14hr by Py4,and 88% in 8hr by the consortium.It was also determined that the best degradation temperatures were 37℃ and pH 7.0 respectively.The influence of different nutrient substrates added in the degradation experiments was also studied.It was shown that sodium salicylate,sodium acetate and yeast exuact had obvious simulative effect,but glucose had no obvious effect.     

Characterization of a Polycyclic Aromatic Hydrocarbon-Degrading Microbial Consortium from a Petrochemical Sludge Landfarming Site

Anthracene, phenanthrene, and pyrene are polycyclic aromatic hydrocarbon (PAHs) that display both mutagenic and carcinogenic properties. They are recalcitrant to microbial degradation in soil and water due to their complex molecular structure and low solubility in water. This study presents the characterization of an efficient PAH (anthracene, phenanthrene, and pyrene)-degrading microbial consortium, isolated from a petrochemical sludge landfarming site. Soil samples collected at the landfarming area were used as inoculum in Warburg flasks containing soil spiked with 250 mg kg^-1 of anthracene. The soil sample with the highest production of CO₂-C in 176 days was used in liquid mineral medium for further enrichment of anthracene degraders. The microbial consortium degraded 48%, 67%, and 22% of the anthracene, phenanthrene, and pyrene in the mineral medium, respectively, after 30 days of incubation. Six bacteria, identified by 16S rRNA sequencing as Mycobacterium fortuitum, Bacillus cereus, Microbacterium sp., Gordonia polyisoprenivorans, two Microbacteriaceae bacteria, and a fungus identified as Fusarium oxysporum were isolated from the enrichment culture. The consortium and its monoculture isolates utilized a variety of hydrocarbons including PAHs (pyrene, anthracene, phenanthrene, and naftalene), monoaromatics hydrocarbons (benzene, ethylbenzene, toluene, and xylene), aliphatic hydrocarbons (1-decene, 1-octene, and hexane), hydrocarbon mixtures (gasoline and diesel oil), intermediary metabolites of PAHs degradation (catechol, gentisic acid, salicylic acid, and dihydroxybenzoic acid) and ethanol for growth. Biosurfactant production by the isolates was assessed by an emulsification index and reduction of the surface tension in the mineral medium. Significant emulsification was observed with the isolates, indicating production of high-molecular-weigh surfactants. The high PAH degradation rates, the wide spectrum of hydrocarbons utilization, and emulsification capacities of the microbial consortium and its member microbes indicate that they can be used for biotreatment and bioaugumentation of soils contaminated with PAHs.     

Non-enzymatic and microsome-dependent binding of polycyclic hydrocarbons to DNA and polynucleotides

The binding of tritium-labelled 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (BP) and 3-methylcholanthrene (MCA) to DNA or polynucleotides in vitro was re-examined both in the presence and in the absence of rat liver or human placental microsomes.A high level of non-enzymatic binding was evident when thymus DNA was used as acceptor. This non-enzymatic binding made it difficult to determine the effect of microsomes, except in the case of BP when induced rat microsomes were used. Better results were obtained using polynucleotides: a definite microsome-dependent binding occurred between all the polynucleotides and all the hydrocarbons tested.No clear evidence of binding catalysed by microsomes from human placenta was found except in polynucleotide-BP interactions: further studies are required to completely evaluate the ability of such nucleic acid-microsomal system for testing in vitro possible oncogenic substances in animals and humans.