Evaluation of the genetic toxicity of middle distillate fuels

Petroleum middle distillate (PMD) fuels are mixtures of hydrocarbons that distill between ～ 170-370°C. Commercial products that fall into this category include kerosine, diesel fuel, jet fuel, and home heating oil. These products contain both saturated (paraffins and cycloparaffins) and aromatic species, but because of the boiling range normally contain very small amounts of the 3-6 ring polycyclic aromatic hydrocarbon (PAH) constituents, which are considered to be carcinogenic. Nevertheless, there is evidence of weak tumorigenic activity when these materials are repeatedly applied to mouse skin. In the current studies representative products were tested in two commonly used, short-term assays for genetic toxicity, the Salmonella/mammalian microsome mutagenicity assay and the mouse bone marrow micronucleus test. All samples were inactive in the micronucleus assay, and three were clearly inactive in the Salmonella test. Of the remaining two, one was marginally active in the Salmonella assay, and one was equivocal. The marginally active sample contained detectable levels of PAH due to the use of catalytically cracked materials as blending stocks. The results indicated that PMDs that do not contain cracked material were not mutagenic. Thus they may produce tumors via nongenotoxic processes. Those products that do contain cracked stocks may have sufficient PAH to be mutagenic in the Salmonella assay, and in those cases the PAH might also contribute to tumor formation. © 1994 Wiley-Liss, Inc.     

祛痹痛注射液的致突变作用观察

用３种不同遗传终点的短期测试方法检测一类新药祛痹痛的致突变作用。Ａｍｅｓ试验是检测基因突变的微生物回复突变试验，微核试验和ＣＨＬ细胞染色体畸变试验分别检测体细胞哺乳动物培养细胞的染色体损伤。结果表明这３种诱变试验均为阴性，提示祛痹痛注射液无致突变性。     

6MVX射线超高剂量照射人离体血淋巴细胞微核的剂量效应研究

本文用CB微核法研究了超高剂量6MVX射线照射人离体血后微核(MN)的剂量效应关系, 见到剂量高至25Gy仍可见双核cB细胞, 在0～10Gy范围内, MN率与照射剂量呈正相关 关系, 并得到拟合较好的回归方程, 有可能打破近30正来生物剂量估算为5 Gy的上限, 使能直接的估算大于5Gy受照者的生物剂量, 摄高了以MN检测作为生物学剂量计的应用价值。10Gy以上, MN串的上升呈平缓的坪趋势, 在10～25Gy范围内虽不能精确的估算剂量, 但片中双核CB细胞的多少, 对判断剂量有—定参考价值。     

免疫荧光染色微核试验检测非整倍体诱变剂

采用免疫荧光染色技术显示微核中的着丝粒，发现纺锤体毒物秋水仙碱诱发Ｖ７９，ＣＨＬ双核细胞徽核着丝粒阳性率分别在７６Ｖ和６６％以上，长春新碱诱发ＢＡＬＢ／ｃ小鼠骨髓红细胞微核着丝粒阳性率在７０％以上；而染色体断裂剂丝裂霉素Ｃ诱发Ｖ７９，ＣＨＬ双核细胞微核着丝粒阳性率分别低于２７％和２１％，环磷酞胺诱发ＢＡＬＢ／ｃ小鼠骨髓红细胞微核着丝粒阳性率低于１５％表明将免疫荧光染色技术与微核试验相结合，计数微核着丝粒阳性率，能够区分微核主要来源于染色体断裂剂引起的无着丝粒断片或纺锤体毒物造成的滞留在胞质中的整条染色体，从而达到简便、快速检测非整倍体诱变剂的目的．     

5—单硝酸异山梨酯的致突变性研究

本文选用Ames试验、小鼠骨髓细胞微核试验和体外细胞染色体畸变试验,对5-单硝酸异山梨酯(5-ISMN)的致突变性进行了研究。Ames试验结果显示,在所选剂量范围内和±S9的条件下,5-ISMN对测试菌株的回复突变菌落数无明显影响,为致突变阴性。在微核试验中,各给药组微核发生率与阴性对照组相比,无显著性差异,P>0.05。染色体畸变试验中也未观察到5-ISMN对体外培养CHL细胞的染色体损伤作用。研究结果表明,5-ISMN对原核生物和哺乳动物细胞无致突变作用。     

三种抗氧化剂对青石棉诱发微核,多核及转化细胞生长的影响

在青石棉诱发Ｖ７９细胞微核与多核模型的基础上，以维生素Ｅ（ＶＥ），β－胡萝卜素（β－Ｃａｒ）或亚硒酸钠（Ｓｅ）分别与青石棉同时处理细胞，观察上述抗氧化剂对其微核细胞率与多核细胞率的影响．发现ＶＥ和Ｓｅ可分别降低其微核细胞率或多核细胞率，β－Ｃａｒ对二者均无影响．采用青石棉诱发的ＢＡＬＢ／ｃ－３Ｔ３恶性转化细胞，观察上述物质对其克隆形成率（ＣＦＥ）和细胞生长的影响．发现Ｓｅ，β－Ｃａｒ和ＶＥ分别在１０，６和２５０μｍｏｌＬ－１以上浓度出现ＣＦＥ降低，且细胞生长受抑．     

氟化氢接触者的诱变研究

测定了密切接触氟化氢工人外周血淋巴细胞的微核（ＭＮ）、姐妹染色单体互换（ＳＣＥ）及血、尿、唾液中的含氟量并分析其与ＭＮ、ＳＣＥ之间的关系。结果表明氟化氢可诱发ＭＮ和ＳＣＥ频率增高；血、尿、唾液含氟量与ＭＮ、ＳＣＥ之间无明显的直线相关关系。     

奥扎格雷钠的致突变作用研究

本文用Ａｍｅｓ试验，微核试验和精子畸形试验对奥扎格雷钠的致突变作用研究，结果表明：①ＯＫＹ－０４６剂量为０．０５、０．５、５、５０、５００μｇ／皿，进行Ａｍｅｓ试验，表明该药未能诱导ＴＡ９８、ＴＡ１００、ＴＡ１０２的回变菌落数增加（ＭＲ〈２）。②ＯＫＹ－０４６药物剂量为３０６．２ｍｇ／ｋｇ，６１２．４ｍｇ／ｋｇ，１２２４．８ｍｇ／ｋｇ时，均不诱发小鼠骨髓嗜多染红细胞的微核率增加。③ＯＫＹ－０４６药     

Re-evaluation of the need for multiple sampling times in the mouse bone marrow micronucleus assay: results for DMBA

7,12-dimethylbenzanthracene (DMBA) is confirmed as active in the mouse bone marrow micronucleus assay 24 hr after dosing as a corn-oil homogenate via either oral gavage or intraperitoneal (ip) injection. These data are consistent with recent observations made by several investigators. However, when dosed via ip injection as a solution in DMSO, peak activity was evident 48 hr after dosing and a dramatic reduction in erythropoiesis was observed. The latter results are consistent with early observations made by Salamone and Heddle. The early observations of Salamone and Heddle were highlighted in the Gene-Tox review of this assay and led the OECD to recommend the use of 3 sampling times for this assay (between 12 and 72 hr). The present data indicate that this advice should be reviewed. In particular, it suggested that a maximum of two sampling times is adequate and that, as a consequence, the number of animals employed in the conduct of the test could be reduced with no loss of sensitivity. The present data also suggest that the use of a corn-oil homogenate of insoluble test agents may provide an efficient replacement for the use of ground suspensions or solutions in DMSO.     

ZnSO4拮抗HgCl2的致小鼠微核作用

本文报道给小白鼠在正常饮食以外,每日补充ZnSO_410.7μmol/kg,6天以上,对HgCl_23.68μmol/kg所致的胸骨微核有显著的拮抗作用。而仅补一次,即ZnSO_4与HgCl_2同时给或先补ZnSO_424h后再给HgCl_2,则拮抗作用不明显,给ZnSO_4的剂量高达61.9μmol/kg,小鼠无致微核作用。而给HgCl_21.84μmol/kg以上,有明显致微核作用。