海南霉素的遗传毒性研究及其致癌性预测：3.海南霉素的致癌性预测

在对海南霉素的遗传毒性进行了系统研究的基础上，本文利用ＣＰＢＳ法进一步预测了其致癌可能性，求得海南霉素的致癌性概率为０．１４％，因而可认为海南霉素为非致癌物。本结论与已有报道的其同类化合物盐霉素和腐霉素等的结论一致。     

Association between Waste Management and Cancer in Companion Animals

Background: Increased cancer rates have been documented in people residing in areas around Naples characterized by illegal dumping and incineration of waste.
Hypothesis: Risk of cancer in dogs and cats is associated with waste management.
Animals: Four hundred and fifty-three dogs and cats with cancer and 1,554 cancer-free animals.
Methods: Hospital-based case-control study in Naples (low danger) and nearby cities having a history of illegal waste dumping (high danger). Odds ratio (OR) between high- and low-danger areas was calculated for all tumors and various malignancies in dogs and cats.
Results: An increased risk for cancer development was identified in dogs but not in cats residing in high-danger areas (OR: 1.55; 95% confidence interval: 1.18–2.03; P < .01). A 2.39-fold increased risk of lymphoma ( P < .01) accounted for the greater tumor frequency in dogs residing in high-danger areas. The risk of mast cell tumor and mammary cancer did not differ in dogs residing in high- or low-danger areas.
Conclusions and Clinical Importance: Waste emission from illegal dumping sites increases cancer risk in dogs residing in high-danger areas. An increased prevalence of lymphoma has been previously recognized in humans living close to illegal waste dumps. Thus, epidemiological studies of spontaneous tumors in dogs might suggest a role for environmental factors in canine and human carcinogenesis and can predict health hazards for humans.     

腐霉素的致突变性研究及其潜在致癌性预测

腐霉素是一种具有抗球虫性能的聚醚类抗生素。本文选择Ａｍｅｓ试验，微核试验和精子畸形试验等三种试验组合来检测腐霉素的致突变性，并在此基础上，用致癌性预测和选择试验组合的方法（ＣＰＢＳ法）预测其潜在致癌性。试验结果表明，腐霉素Ａｍｅｓ试验，微核试验和精子畸形成试验均为阴性；ＣＰＢＳ法预测霉素可能是潜在致癌物的概率为８．５２％，因而被评为非致癌物。     

新型饲料添加剂喹胺醇致突变性及其潜在致癌性预测

 选择Ａｍｅｓ试验、小鼠微核试验和精子畸形试验３种短期试验组合研究了喹胺醇的致突变性,并在获得各 单项试验结果的基础上,利用“致癌性预测和选择试验组合的方法”即 ＣＰＢＳ法对喹胺醇潜在致癌性进行预测。结果表 明：（１）Ａｍｅｓ试验喹胺醇标准掺入不论加与不加Ｓｇ－ｍｉｘ对鼠伤寒沙门氏菌 ＴＡ９８和ＴＡ１００两个标准株都有诱变性,并 有剂量－反应关系。加入 Ｓｇ－ｍｉｘ后,ＴＡ９８和 ＴＡ１００回复突变菌落数均明显下降。（２）小鼠处死前 ３０ｈ和 ６ｈ分别腹腔注 射哇胺醇３０,６０,１２０和２４０ｍｇ／ｋｇ,骨髓嗜多染红细胞（ＰＣＥ）微核率与阴性对照组（５０％ＤＭＳＯ）比较差异均不显著（Ｐ ＞０．０５）。（３）小鼠连续用哇胺醇４５０、７５０、１０００和１５００ ｍｇ／ｋｇ灌胃５ｄ（１次／ｄ）,于第３５天处死,精子畸形率与阴性对 照组（２％吐温－８０）比较差异均不显著（Ｐ＞０．０５）。（４）利用ＣＰＢＳ法预测,喹胺醇θ＝０．２３８,初步定为非致癌物,进一步 的结论还需增加试验组合进行确定。     

Studies on the Mutagenicity and Teratogenicity of Kuianchun and Its Potential Carcinogenicity Prediction

Kuianchun is a newly synthesized antibacterial and growth-promoting drug. This paper selected a battery of three short-term tests, including Ames test, micronucleus test and sperm abnormality test, to detect the mutagenicity of Kuianchun. The carcinogenicity prediction and battery selection method (CPBS method) was used to determine the probability of carcinogenicity of Kuianchun based upon the results of shortterm tests mentioned above. In addition, traditional teratogenic test was selected to study teratogenicity of Kuianchun. In Ames test, Kuianchun showed mutagenic for Salmonella typhimurium strains TA98 and TA100 in the absence and presence of microsomal metabolic activation system (S9-mix). However, the mutagenicity was reduced by the addition of S9-mix. In micronucleus test, Kuianchun was administered intra-peritoneally to male mouse 30 hours and 6 hours before they were killed respectively. The result indicated that there was no significant difference on the number of micronucleated polychromatic erythrocytes (PCEs) in the mouse bone marrow induced by Kuianchun compared with the negative contrast (50% DMSO) (P ＞ 0.05). In sperm abnormality test, Kuianchun was administered through a gastric incubation to male mouse as a suspension in 2% Tween-80. The dosage levels were 450, 750, 1000 and 1500mg/kg per day for 5 days. The result indicated that the percentage of abnormal sperms induced by Kuianchun was not significant compared with the negative contrast (P＞0.05). In traditional teratogenic test, Kuianchun was given orally to pregnant mouse at 1/30,1/20 and 1/15 LDs0 during 6 - 15days of pregnancy period (the LD50 = 9000mg/kg). No toxicity was found either on mother and embryo in mouse, and teratogenic effects were also not observed at all tested dosages. The probability of carcinogenicity of Kuianchun is 23.8 % (θ = 0.238). The result demonstrated that Kuianchun is a non-carcinogen.     

诱导多能干细胞(iPSCs)及其医疗应用的研究进展

诱导多能干细胞(induced pluripotent stem cells)的研究是现阶段生命科学领域的热点之一,它建立了一种全新的、相对易操作而较稳定的体细胞核重编程方法,在生物学基础研究和临床应用方面具有潜在的价值。然而,研究过程中发现iPS细胞存在诱导频率过低、致瘤性、临床应用安全等一系列问题。目前,iPS细胞的研究主要集中于诱导方法的优化、iPS细胞转化率的提高以及iPS细胞癌变风险的降低等方面,并且在多个领域取得了重大突破。文中主要综述了iPS细胞的研究历程、iPS细胞的最新研究进展及其在医疗领域的应用前景。