DNA damage from polycyclic aromatic hydrocarbons measured by benzo[a]pyrene-DNA adducts in mothers and newborns from Northern Manhattan, the World Trade Center Area, Poland, and China.

Polycyclic aromatic hydrocarbons (PAH), of which benzo[a]pyrene is a representative member, are combustion-related environmental pollutants and include known carcinogens. Laboratory animal studies indicate that the dose of PAHs to the fetus is on the order of a 10th that to the mother and that there is heightened susceptibility to PAH-induced carcinogenesis during the fetal and infancy periods. Carcinogen-DNA adducts, a measure of procarcinogenic genetic damage, are considered a biomarker of increased cancer risk. Here we compare the levels of benzo[a]pyrene-DNA adducts as a proxy for PAH-DNA damage measured in maternal blood and newborn cord blood obtained at delivery in four different populations of mothers (total of 867) and newborns (total of 822), representing a 30-fold range of exposure to ambient PAHs. The populations include residents in Northern Manhattan, participants in a study of the effects of the World Trade Center disaster, residents in Krakow, Poland, and residents in Tongliang, China. Mean adduct concentrations in both maternal and cord blood and the proportion of samples with detectable adducts, increased across the populations [Northern Manhattan < World Trade Center (WTC) < Krakow < Tongliang], consistent with the trend in estimated ambient exposure to PAHs (P < 0.001). For mothers, the means in the respective populations were Northern Manhattan (0.21 adducts per 10(8) nucleotides), WTC (0.23 adducts per 10(8) nucleotides), Krakow (0.28 adducts per 10(8) nucleotides), Tongliang (0.31 adducts per 10(8) nucleotides); the corresponding means in the newborns were Northern Manhattan (0.23), WTC (0.24), Krakow (0.29), Tongliang (0.31). The percentage of mothers with detectable levels of adducts in the respective populations were Northern Manhattan (36.8%), WTC (57.5%), Krakow (72.9%), Tongliang (73.4%); the corresponding percentages among the newborns were Northern Manhattan (42.4%), WTC (60.6%), Krakow (71.1%), Tongliang (79.5%). Despite the estimated 10-fold lower PAH dose to the fetus based on laboratory animal experiments, the adduct levels in the newborns were similar to or higher than in the mothers. This study suggests that the fetus may be 10-fold more susceptible to DNA damage than the mother and that in utero exposure to polycyclic aromatic hydrocarbons may disproportionately increase carcinogenic risk. The data support preventive policies to limit PAH exposure to pregnant women and children.     

Utility of the coefficient of determination (r2) in assessing the accuracy of interspecies allometric predictions: illumination or illusion?

The appropriateness of relying on the coefficient of determination (r(2)) as a statistical metric for judging the predictability of human clearance (CL) based on interspecies animal data was assessed. An explicit mathematical expression was derived for r(2) as a function of species body weight and the corresponding measured value of CL. The derived mathematical function demonstrated that r(2) is numerically large in most instances. Simulations using random CL generated from a common combination of species of mouse, rat, and monkey resulted in an r(2) of 0.75 as the minimum, and 0.95 and 0.98 at 50th and 75th percentiles, respectively, given that total CL values increase with increasing species body weight. Analysis of literature data also indicated that the prediction accuracy of human CL was not correlated with values of r(2). Therefore, it is concluded that r(2) is a limited statistical measure when assessing allometric scaling for the purpose of predicting human CL.     

TNF-α和低氧对胰腺癌细胞表达VEGF-A、C的调节

目的:探讨细胞活素肿瘤坏死因子-α(TNF-α)、SNAP(S-Nitroso-Nacetyl-penicillamine)对胰腺癌细胞产生血管内皮生长因子A、C(VEGF-A、C)的调节.方法:用Northern杂交和Western杂交法分析6种人胰腺癌细胞株中VEGF-A、C基因和蛋白的表达;以TNF-α或SNAP刺激其中两个细胞株后用逆转录-聚合酶链式反应技术(RT-PCR)分析其VEGF-A、C基因的表达.结果:Northern杂交法显示这6种胰腺癌细胞株均有4.1kb VEGF-A基因和2.4kb VEGF-C基因的表达;Western杂交法显示它们均有分子量为43kD的VEGF-A蛋白质和分子量为55kD的VEGF-C蛋白质的表达.RT-PCR分析法显示:TNF-α使细胞株COLO-357产生VEGF-A、VEGF-C mRNA分别减少约1～2.5倍、1～2倍,使细胞株CAPAN-1产生VEGF-A、VEGF-C mRNA分别减少约1倍、1.6～2.5倍;而SNAP刺激细胞株COLO-357产生VEGF-A mRNA增加约5倍,刺激细胞株CAPAN-1产生VEGF-A mRNA增加约4倍,但对这两种细胞株产生VEGF-C mRNA均无明显刺激作用.结论:细胞活素TNF-α和低氧通过调节血管内皮生长因子A、C的表达而影响胰腺癌细胞的生物学特性,抑制癌细胞的增殖,促进其凋亡、死亡或进展、恶化.     

改制先改革,改革先改人宿迁医改的政府内应力

“人民,是创造历史的真正动力”——壮哉斯言；“真理,只掌握在少数人手中”——诚哉斯言。尽管发生在苏北宿迁的这场席卷城乡的改革,绝不可能只由少数精英分子独立完成,但最初的推动力,是全民意志的厚积薄发?是少数精英的灵光一闪?抑或是一场上级授权、政府定规、全民参与的社会实验?     

Schedule-induced cocaine drinking: choice between cocaine and vehicle

Rats were exposed to daily 3-hr schedule-induced polydipsia sessions (fixed-time 1-min food-pellet delivery) with two drinking fluids available: cocaine solution and water. Fluid position was alternated daily. Polydipsia occurred mostly from a preferred-side spout (position preference) until cocaine solution concentration was increased to between 0.52 and 1.04 mg/ml and animals drank mostly water. Within a lower concentration range (0.28-0.6 mg/ml) maximum session cocaine intakes ranged from 54.3 to 120.1 mg/kg. Postsession serum cocaine levels were about 200 ng/ml. At individually chosen cocaine solution concentrations, the addition of saccharin to the solution did not increase cocaine intake, but a compound solution (saccharin plus glucose) did. With progressive dilution of the compound vehicle, an almost complete preference for cocaine solution was maintained. But with a return to water as the vehicle, animals reverted to a position preference after a few sessions, although one maintained a clear cocaine preference. Schedule-induced polydipsia produced chronic, oral self-administration of cocaine resulting in pharmacologically significant intakes and serum levels.     

谷氨酸诱导体外培养的鸡胚脊髓神经细胞释放NO

用鸡胚脊髓神经细胞的原代培养,测定细胞中亚硝酸盐的含量,研究了谷氨酸(Glu)对原代培养神经细胞中NO的影响。结果表明,谷氨酸作用于原代培养的鸡胚脊髓神经细胞,在诱导神经细胞释放乳酸脱氢酶(LDH)的同时,还可诱导细胞释放一氧化氮(NO)。如先用NO合成酶抑制剂L-NOARG作用细胞,再加入Glu,则发现L-NOARG能降低Glu导致的培养液中LDH活性升高。提示NO可能参与介导Glu的神经毒性作用。     

对一宗入境二级放射货包的监测结果分析

汕头卫生检疫局空港处对汕头航空口岸—宗入境二级货包的监测过程及对有关运输工作人员作了放射知识问卷调查。从中发现。运输单位货物存放设施落后。有关工作人员放射卫生知识欠缺，对放射污染可能造成的危害缺乏正确的认识。为此，笔者提出了自己的看法，以期对放射监测工作的进一步完善提供参考。     

纤维支气管镜胸膜腔检查对原因不明胸腔积液的诊断价值

为评价纤维支所管镜行胸膜检查在诊断原因不明胸腔积液中的价值，用纤维支气管镜对１０例原因不明的胸腔积液患者进行胸腔检查。结果９例２检查后明确了病因，且无并发症，提示该法对于不明胸腔积液的诊断是一种阳性率高、安全、简便的检查方法。     

锗元素与抗肿瘤药物(Ⅱ)(续上期)

综述了有机锗抗肿瘤药物，对β－羧乙基锗倍半氧化物（Ｇｅ－１３２）和螺锗在肿瘤学中的作用以及抗癌效应机制作出评价。自８０年代起至今，又有含硫杂、柠檬酸、氨基酸、苯基的锗化合物，以及锗酵母、含锗中草药等被先后合成出来。在几类具有生物活性的有机锗化合物中，仍首推Ｇｅ－１３２，螺锗及其衍生物为低毒有效抗肿瘤候选药物，然而对于锗导致的毒性及其机理仍需进一步加以探讨。