Subcellular localization of glutaraldehyde

Abstract Glutaraldehyde (GA) has been proposed as an alternative to formocresol for pulpotomies in primary teeth and as an irrigant in root canal therapy. These studies were undertaken to determine if GA can associate with the nucleus of living cells, thereby posing a mutagenic threat. Rats were infused IV with ¹⁴C-GA and killed 5 min and 1 h later. The cystolic, membrane, and nuclear fractions of harvested liver cells were separated and analyzed for radioactivity. We determined that significant radioactivity was located in the cytosol and membrane fractions, but not in the nuclear fraction. In an in vitro experiment, liver slices were incubated with ¹⁴C-GA in sealed vials in which ¹⁴C-CO₂ was captured. After 1 h the nucleic acids of the liver slices were isolated and counted. In vitro the liver cells incorporated and metabolized GA to CO₂ but no significant label could be detected in the isolated nucleic acids. We concluded from these experiments that GA which was incorporated into liver cells did not reach the nucleus to a significant extent, and that its potential for mutagenicity in the context of pulp treatment was nil.     

氯硝柳胺对鼠伤寒沙门氏菌致突变试验

本文采用鼠伤寒沙门氏菌诱变性试验（Ａｍｅｓ试验）．对新型长效杀螺剂－氯硝柳胺控释剂主药氯硝柳胺进行了致突变作用的研究。在最小抑菌剂量４０μｇ／Ⅲ以下０．１２５－８μｇ／Ⅲ范围内，实验证明无致突变作用。     

Genetic toxicology in the 21st century: reflections and future directions

A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high‐throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U.S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast?, a related research program of the U.S. Environmental Protection Agency, using a broad array of high throughput and high content technologies for toxicity profiling of environmental chemicals, and computational toxicology modeling. Progress and challenges, including the pressing need to incorporate metabolic activation capability, are summarized. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc.     

蛞蝓胶囊致畸和致突变实验研究

目的探讨蛞蝓胶囊是否具有致畸和致突变的毒理作用。方法本研究采用大鼠致畸胎、艾姆斯（Ames）试验、小鼠骨髓细胞微核试验、体外细胞染色体畸变试验检测的蛞蝓胶囊致畸胎、致突变性。结果蛞蝓胶囊各剂量对孕鼠体重、胚胎早期发育、胚胎生长发育、以及胎鼠的骨骼发育和内脏器官发育等均无不良影响。无论加与不加S9,各剂量组诱变TA98、TA100种菌落数均未超过自然回变菌落数,与阴性对照组比较均无显著性差异（P〉0．05）。与对照组相比,各剂量组对小鼠的微核率无明显的影响（P〉0．05）。蛞蝓胶囊对培养的哺乳动物体细胞染色体结构无致畸变作用。结论蛞蝓胶囊各剂量均无致畸和致突变的作用,说明在临床应用剂量范围内是安全的。     

Mutagenicity studies with N-acetyl-l-aspartic acid

Analytical studies have reported that N-acetyl-l-aspartic acid (NAA) is present at low concentrations in many foods. The current studies were conducted to assess the mutagenicity of NAA using standard OECD guideline in vitro bacterial and in vivo mammalian mutagenicity studies. For comparison and control data, mutagenicity studies were also conducted with its constituent amino acid l-aspartate (ASP) because NAA is metabolized to ASP. The combination of an in vitro method for assessing point mutations in bacteria and an in vivo method to assess clastogenicity in an animal model provided adequate evidence for mutagenicity hazard assessment of NAA. No evidence of mutagenicity was observed in either test system with either NAA or ASP. The results from the current studies demonstrate that the presence of NAA in foods is not likely to represent a risk for mutagenicity.     

The impact of differential lignin S/G ratios on mutagenicity and chicken embryonic toxicity

Lignin and lignin-based materials have received considerable attention in various fields due to their promise as sustainable feedstocks. Guaiacol (G) and syringol (S) are two primary monolignols that occur in different ratios for different plant species. As methoxyphenols, G and S have been targeted as atmospheric pollutants and their acute toxicity examined. However, there is a rare understanding of the toxicological properties on other endpoints and mixture effects of these monolignols. To fill this knowledge gap, our study investigated the impact of different S/G ratios (0.5, 1, and 2) and three lignin depolymerization samples from poplar, pine, and miscanthus species on mutagenicity and developmental toxicity. A multitiered method consisted of in silico simulation, in vitro Ames test, and in vivo chicken embryonic assay was employed. In the Ames test, syringol showed a sign of mutagenicity, whereas guaiacol did not, which agreed with the T.E.S.T. simulation. For three S and G mixture and lignin monomers, mutagenic activity was related to the proportion of syringol. In addition, both S and G showed developmental toxicity in the chicken embryonic assay and T.E.S.T. simulation, and guaiacol had a severe effect on lipid peroxidation. A similar trend and comparable developmental toxicity levels were detected for S and G mixtures and the three lignin depolymerized monomers. This study provides data and insights on the differential toxicity of varying S/G ratios for some important building blocks for bio-based materials.     

19种有机磷农药对酵母D61.M菌株的诱变性

本文利用检测染色体丢失的酵母D61.M菌株对19种有机磷农药进行诱变性研究，并与本室过去利用其他两种诱变试验结果进行对比分析. 结果表明D61.M的检出率为89.5%(17/19)，即提示大多数有机磷农药可诱发非整倍体. 17种呈阳性的有机磷农药中有14种也能在体外微核试验中检出，它们可能单独引起非整倍体或兼能引起染色体断裂. 仅两种有机磷农药(乙硫磷，乙拌磷)单独在微核试验中检出而被D61.M漏检，提示只有少数有机磷农药单独具有断裂作用. 经进一步比较体内，体外微核试验及对甲基，乙基和其他有机磷农药的测试结果，提示D61.M对脱甲基以及“脱芳基”的能力最差.     

常用抗癌药物诱发人外周血淋巴细胞核损伤的观察

本文用阿霉素、阿糖胞苷、氟尿嘧啶、氮芥及秋水仙素和长春新碱体外处理人外周血淋巴细胞，观察了这七种具诱变作用的抗癌药诱发的微核、核变形、核碎裂等核损伤变化。结取表明，七种抗癌药物均能引起多种核损伤指标的改变，并呈剂量依赖性增加，其中微核率、核异常率最明显。本实验结果并综合文献讨论后作者认为：应用核异常测试法评价化学诱变因子对人体的遗传毒性和潜在致癌性是可行的。     

绿乳铜毒性的实验研究

绿乳铜的急性经口ＬＤ５０，雄性大鼠为５９４６ｍｇ／ｋｇ，雌性大鼠为７３２１ｍｇ／ｋｇ，性别间差异没有显著性；而在雄性与雌性小鼠则分别为３４８０ｍｇ／ｋｇ和７９４０ｍｇ／ｋｇ。大鼠急性经皮ＬＤ５０大于２０００ｍｇ／ｋｇ。与此同时，Ａｍｅｓ试验、小鼠骨髓嗜多染红细胞微核试验和小鼠睾丸精母细胞染色体畸变试验结果均呈阴性。结果表明绿乳铜属低毒类杀菌剂，且对体细胞与生殖细胞未发现致突变性，其应用比较安全。然而，绿乳铜的蓄积系数为３．８，具中等蓄积毒性，故应该加强对长期接触者的健康保护，以防慢性中毒的发生。