染苯小鼠DNA加合物的形成与剂量－反应关系

染苯小鼠ＤＮＡ加合物的形成与剂量－反应关系王春光，李桂兰，尹松年苯能导致骨髓造血组织的多种疾患且具致癌作用。我们曾以３２Ｐ后标记方法就腹腔注射染苯小鼠体内ＤＮＡ加合物的形成及持续时间进行了探讨，发现苯在体内可至少形成２种加合物［１］．然而小鼠吸入染苯...     

皮蛋国家卫生标准制准制修订研究报告

本文对７７５份皮蛋的卫生指标进行了测定，卫生指标含量范围铅为０—５／Ｋｇ，砷为０—１１．２／Ｋｇ，铜为０．７－１７．５０ｍｇ／ｋｇ，锌为３．８－３５／ｋｇ，ＰＨ为８．５０－１１．５。参考国家卫生标准ＧＢ５１２８—８５、ＧＢ９６９４—８８标准，提出皮蛋卫生标准理化指标为传统工艺生产的皮蛋铅为≤２ｍｇ／ｋｇ，砷为≤为０．５ｍｇ／ｋｇ，ＰＨ为≥９．５０；非传统生产的皮蛋铅为≤０．５ｍｇ／ｋｇ，砷为≤０．５ｍｇ／ｋｇ，铜为≤１０ｍｇ．ｋｇ，锌为≤２０ｍｇ／ｋｇ；微生物指标：菌落总数≤５００个／ｍｌ，大肠菌群为≤３０个ＭＰＮ／１００ｍｌ，致病菌不得检出。     

苯DNA加合物的组织分布及其与细胞遗传毒性的关系

用Ｐ１增强的３２Ｐ－后标记方法测定了经腹腔注射染苯小鼠不同组织ＤＮＡ加合物的分布及其与苯引起的外周血白细胞（ＷＢＣ）减少、淋巴细胞微核形成及骨髓细胞染色体畸变的关系。结果表明：１．苯在小鼠骨髓、肝脏和外周血ＷＢＣ均可形成ＤＮＡ加合物，其加合物含量以骨髓最高，肝脏次之，ＷＢＣ最低。本结果与苯的代谢及毒性作用特点相一致。２．ＤＮＡ加合物形成与细胞毒性有关系，ＤＮＡ加合物量增加，淋巴细胞微核及骨髓细胞染色体畸变亦增加，而外周血白细胞数明显减少，显示细胞遗传毒性和细胞毒性均增大。本研究为ＤＮＡ加合物作为生物学监测指标，筛选高危人群提供了有力的实验依据。     

DDC与平阳霉素联合应用治疗小鼠P388肿瘤的实验研究

应用小鼠Ｐ３８８实体瘤模型，进行了二乙基二硫代氨基甲酸钠（ＤＤＣ）增强平阳霉素（ＢＬＭＡ５）抗癌活性的实验。结果表明，在ＢＬＭＡ５１２ｍｇ／ｋｇ、１５ｍｇ／ｋｇ及２４ｍ／ｋｇ３个剂量组分别辅加５００ｍｇ／ｋｇＤＤＣ后，抑癌率明显高于单独用ＢＬＭＡ５的试验组。给小鼠ｉｐ５００ｍｇ／ｋｇ、７５０ｍｇ／ｋｇＤＤＣ，在３０ｍｉｎ、１ｈ、４ｈ时，受试小鼠的ＳＯＤ活性丧失至０，到２４ｈ时，ＳＯＤ活性才恢复到正常的４０％。结果提示，减少Ｃｕ２＋的水平及增加Ｏ＿２￣－的浓度可以修饰ＢＬＭＡ５的细胞毒性。     

硒和锗拮抗苯致小鼠骨髓细胞微核的实验观察

采用小鼠骨髓嗜多染红细胞微核试验方法观察微量元素硒和锗的抗苯诱变活性。结果：苯吸入染毒（１５ｍｇ／Ｌ×５天，每天２小时）后，小鼠微核率明显增高。在苯处理前３０分钟经口给予不同浓度的亚硒酸钠（００５～２５０ｍｇ／ｋｇ）或锗－１３２（５０～５００ｍｇ／ｋｇ），微核细胞率显著降低，微核抑制率随硒或锗剂量的增加而升高。提示，硒和锗对苯诱导的遗传物质损伤具有保护作用     

氟化钠,氯化汞和亚砷酸钠对小鼠睾丸早期精细胞微核率的影响

采用Ｔａｔｅｓ微核试验法检测３种无机化学物对雄性小鼠生殖细胞染色体的损伤作用。不同剂量的氟化钠（１４ｍｇ／ｋｇ、２８ｍｇ／ｋｇ）、氯化汞（０．５ｍｇ／ｋｇ、１．０ｍｇ／ｋｇ）和亚砷酸钠（０．２５ｍｇ／ｋｇ、０．５ｍｇ／ｋｇ）分别经腹腔注射染毒，每天１次，连续３天，于首次染毒后第１５天杀鼠。测得微核率为７．２％，１０．０‰；６．４‰、５．６‰和３．４‰、３．０‰。其中氟化钠和氯化汞组的微核率与阴性对照组（２．２‰）比较．有显著差异．可以认为是雄性生殖细胞染色体断裂剂。根据染毒到制片的间隔时间判断，氟化钠和氯化主要作用于减数分裂前的Ｇ１和Ｓ期初级精母细胞。     

氯化镉对小鼠精子的影响

４０只小鼠随机分为４组：对照组，氯化镉３．５ｍｇ／ｋｇ，氯化镉７．０ｍｇ／ｋｇ，氯化镉１４．０ｍｇ／ｋｇ。灌胃染毒，灌胃量为０．１ｍｌ／１０ｇ体重。３天后处死动物，检测精子活动率及精子密度。结果表明，氯化镉７．０ｍｇ／ｋｇ和氯化镉１４．０ｍｇ／ｋｇ组精子活动率比对照组降低（Ｐ〈０．０５），氯化镉７．０ｍｇ／ｋｇ和氯化镉１４．０ｍｇ／ｋｇ组精子密度比对照组降低有非常显著意义（Ｐ〈０．０１）。     

皮蛋国家卫生标准制修订研究报告

本文对７７５份皮蛋的卫生指标进行了测定，卫生指标含量范围铅为０－５ｍｇ／ｋｇ砷为０－１１．２ｍｇ／ｋｇ，铜为０．７－１７．５０ｍｇ／ｋｇ，锌为３．８－３５ｍｇ／ｋｇ，ｐＨ为８．５０－１１．５，参考国家卫生标准ＧＢ５１２８－８５，ＧＢ９６９４－８８标准，提出皮蛋卫生管理理化指标为传统工艺生产的皮蛋铅为≤２ｍｇ／ｋｇ，砷为≤０．５ｍｇ／ｋｇ，ｐＨ为≥９．５０；非传统生产的皮蛋铅为≤０．５ｍｇ／ｋｇ，砷     

霉敌的安全性毒理学评价

为了评价霉敌（１，２－苯并异噻唑啉酮的安全性，对其进行了急性毒性、蓄积毒性、Ａｍｅｓ、ＤＮＡ重组、小鼠微核、小鼠精子畸变、大鼠传统致畸和大鼠９０天喂养等试验。结果表明：霉敌属低毒物质，有中等蓄积毒性，无致突变、致畸作用。大鼠９０天喂养最大无作用剂量为３２．４ｍｇ／ｋｇ，建议ＡＤＩ为０．３２ｍｇ／ｋｇ。     

一种有机镓化合物对小鼠的胚胎毒性和致畸性

本文报道２－二甲氨基环己氧基－二甲基镓的胚胎毒性和致畸性的试验结果。雌性小鼠在检出阴栓的当天定为妊娠ｄ０，于ｄ０～ｄ１５每天灌胃一次，剂量分１．５，３，６ｍｇ／ｋｇ三组，对照组给生理盐水，ｄ１７处死小鼠剖腹按常规方法检查胚胎毒性和致畸性。结果表明６ｍｇ／ｋｇ组２只母鼠中毒死亡，各染毒组母鼠体重增长迟缓。３和６ｍｇ／ｋｇ组出现明显胚胎毒性，早期吸收胎明显增加。染毒组活存胎鼠中均有外观、骨骼和内脏畸形可见。     

苯和硒对小鼠淋巴细胞端粒酶活力的影响

目的 研究苯和硒对小鼠淋巴细胞端粒酶活力的影响,评价端粒酶作为苯刺激淋巴细胞的早期效应标志物的可能性.方法 健康雄性昆明种小鼠随机分为阴性对照组,溶剂对照组,100、200、400 mg/kg苯组,200 mg/kg苯+0.75 ms/ks亚硒酸钠组,200 mg/kg苯+1.50 mg/kg亚硒酸钠组,200 ms/kg苯+3.00mg/kg亚硒酸钠组,每组5只.各组分别给予不同处理,共5 d,每天1次.最后1次染毒48 h后,分离淋巴细胞,用端粒重复扩增一酶联免疫吸附(TRAP-ELISA)法检测端粒酶活力.结果 各剂量苯组的端粒酶活力均增加,与阴性对照组和溶剂对照组比较,其中,100mg/kg苯组差异有统计学意义(P＜0.01).各剂量苯联合硒组的端粒酶活力均增加,与阴性对照组和溶剂对照组比较,200 mg/kg苯+0.75mg/kg亚硒酸钠组差异有统计学意义(P＜0.01);与相应的200 mg/kg苯组比较,200 mg/kg苯+0.75 mg/kg亚硒酸钠组差异有统计学意义(P＜0.05).结论 不同浓度的苯刺激的端粒酶活力均增加,表明小鼠淋巴细胞得到激活和增殖.端粒酶可能是苯刺激淋巴细胞的一种敏感的早期效应标志物.硒可以上调小鼠淋巴细胞端粒酶活力.     

Effects of dietary conjugated linoleic acid on DNA adduct formation of PhIP and IQ after bolus administration to female F344 rats

Meats cooked at high temperatures contain mutagenic heterocyclic amines such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). In female Fischer 344 rats, IQ is a multiorgan carcinogen, whereas PhIP induces mammary adenocarcinomas. For IQ and PhIP, N-hydroxylation, catalyzed by microsomal cytochrome P-450 1A1 and/or 1A2, and then esterification, especially O-acetylation, are the principal steps leading to DNA adduct formation. Conjugated linoleic acid (CLA) is a mixture of conjugated linoleic acid isomers found in various meat and dairy products. We have examined the effect of dietary CLA on DNA adduct formation by PhIP and IQ in female Fischer 344 rats. Four-week-old animals were maintained on AIN-76A diet without or with CLA (4% wt/wt) and treated with IQ or PhIP (50 mg/kg by gavage) after two weeks. Animals were killed (4/group) one, four, and eight days later. DNA isolated from mammary epithelial cells, liver, colon, and white blood cells was analyzed for carcinogen-DNA adducts by 32P-postlabeling assays. On Day 1, dietary CLA significantly inhibited adduct formation (82.0%) in mammary epithelial cells in IQ--but not in PhIP-treated rats. In the colon, dietary CLA significantly inhibited PhIP-DNA adduct formation (18.7%) on Day 8 but increased IQ-DNA adduct formation (30.5%) on Day 8. Dietary CLA had no effect on adduct levels in liver or white blood cells. Calf thymus DNA was incubated with N-hydroxy-PhIP or -IQ in the presence of acetyl-CoA. Enzymatic activation was catalyzed by liver or mammary cytosol. A two-week pretreatment with 2% (wt/wt) dietary CLA had no effect on O-acetyltransferase-catalyzed IQ- or PhIP-DNA adduct formation. It is concluded, under certain conditions, that dietary CLA can lower IQ- and PhIP-DNA adduct formation. Overall, however, the major mode of action of CLA is probably by a mechanism other than the inhibition of the N-hydroxylation and subsequent O-acetylation of PhIP or IQ.     

Effects of dietary conjugated linoleic acid on DNA adduct formation of PhIP and IQ after bolus administration to female F344 rats

Meats cooked at high temperatures contain mutagenic heterocyclic amines such as 2‐amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ). In female Fischer 344 rats, IQ is a multiorgan carcinogen, whereas PhIP induces mammary adenocarcinomas. For IQ and PhIP, N‐hydroxylation, catalyzed by microsomal cytochrome P‐450 1A1 and/or 1A2, and then esterification, especially O‐acetylation, are the principal steps leading to DNA adduct formation. Conjugated linoleic acid (CLA) is a mixture of conjugated linoleic acid isomers found in various meat and dairy products. We have examined the effect of dietary CLA on DNA adduct formation by PhIP and IQ in female Fischer 344 rats. Four‐week‐old animals were maintained on AIN‐76A diet without or with CLA (4% wt/wt) and treated with IQ or PhIP (50 mg/kg by gavage) after two weeks. Animals were killed (4/group) one, four, and eight days later. DNA isolated from mammary epithelial cells, liver, colon, and white blood cells was analyzed for carcinogen‐DNA adducts by ³²P‐postla‐beling assays. On Day 1, dietary CLA significantly inhibited adduct formation (82.0%) in mammary epithelial cells in IQ‐but not in PhIP‐treated rats. In the colon, dietary CLA significantly inhibited PhIP‐DNA adduct formation (18.7%) on Day 8 but increased IQ‐DNA adduct formation (30.5%) on Day 8. Dietary CLA had no effect on adduct levels in liver or white blood cells. Calf thymus DNA was incubated with N‐hydroxy‐PhIP or ‐IQ in the presence of acetyl‐CoA. Enzymatic activation was catalyzed by liver or mammary cytosol. A two‐week pretreatment with 2% (wt/wt) dietary CLA had no effect on O‐acetyltransferase‐catalyzed IQ‐ or PhIP‐DNA adduct formation. It is concluded, under certain conditions, that dietary CLA can lower IQ‐ and PhlP‐DNA adduct formation. Overall, however, the major mode of action of CLA is probably by a mechanism other than the inhibition of the N‐hydroxylation and subsequent O‐acetylation of PhIP or IQ.     

氧化乐果对小鼠精子DNA损伤的研究

目的 研究有机磷农药氧化乐果对雄性小鼠精子DNA的损伤作用.方法 将18～20 g清洁级昆明种雄性小鼠按体重随机分为氧化乐果低(0.5 mg/kg)、中(1 mg/kg)、高(2 mg/kg)剂量组和对照组(等体积生理盐水),每组10只.每天灌胃染毒1次,连续35 d.染毒后,称量体重,取出睾丸和附睾、称重,计算睾丸系数.采用彗星试验检测小鼠精子DNA的损伤情况,采用Nikon荧光显微镜和图像采集卡进行拍照,用MIM软件对所拍摄的图像进行分析,以评估精子细胞DNA受损伤程度.结果 随着氧化乐果染毒剂量的增加,小鼠体重、睾丸重量以及睾丸系数均呈下降趋势,但差异均无统计学意义(P＞0.05);良好精子的构成比和精子密度呈下降趋势,死亡精子的构成比和精子畸形率呈上升趋势;彗星长度、彗星重心、尾长、尾重心、Olive尾矩、尾惯量、尾长/头长、尾部DNA含量均呈上升趋势.精子畸形主要以胖头和尾折叠为主.结论 氧化乐果对小鼠精子DNA有明显的损伤作用.     

硝酸镧染毒对小鼠骨髓细胞微核率的影响

目的研究硝酸镧染毒对小鼠骨髓细胞微核率的影响。方法将21日龄昆明种小鼠随机分为9组,每组12只,分别腹部皮下注射不同剂量的硝酸镧溶液(10、50、100、200、300、400、500mg/kg),阴性对照组给予蒸馏水,阳性对照组给予环磷酰胺,每天1次,连续7d,观察小鼠骨髓细胞微核率及小鼠体重。结果300、400、500mg/kg组小鼠增重低于阴性对照组,差异有显著性(P<0.05)。100、200、300、400、500mg/kg组小鼠骨髓细胞微核率高于阴性对照组(P<0.05)。随染毒剂量增加,小鼠骨髓细胞微核率呈上升趋势(r=0.9223P<0.05)。结论硝酸镧具有一定遗传毒性。     

Identification of 6-hydroxy-trans,trans-2,4-hexadienoic acid, a novel ring-opened urinary metabolite of benzene.

We studied the in vivo metabolism of benzene in mice to ring-opened compounds excreted in urine. Male CD-1 mice were treated intraperitoneally with benzene (110-440 mg/kg), [14C]benzene (220 mg/kg) or trans, trans-muconaldehyde (MUC; 4 mg/kg), a microsomal, hematotoxic metabolite of benzene. Urine, collected over 24 hr, was extracted and analyzed by HPLC with a diode-array detector and by scintillation counting. In addition to trans,trans-muconic acid, previously the only known ring-opened urinary benzene metabolite, a new metabolite, 6-hydroxy-trans,trans-2,4-hexadienoic acid, was detected in urine of mice treated with either benzene or MUC. We identified the new metabolite based on coelution of metabolites and UV spectral comparison with authentic standards in unmethylated and methylated urine extracts. Results presented here are consistent with the intermediacy of MUC in the in vivo metabolism of benzene to ring-opened metabolites.     

Inhaled crocidolite mutagenicity in lung DNA

We used transgenic mice carrying the lacI reporter gene to study the mutagenesis potential of asbestos crocidolite. The animals were exposed by nose-only inhalation to an aerosol containing 5.75 mg/m(3) crocidolite dust for 6 hr/day and 5 consecutive days. After 1, 4, and 12 weeks, we examined four end points: the cytology of bronchoalveolar lavage, the lung load of crocidolite, the hydrophobic DNA adducts, and the mutations in the lacI reporter gene. Twelve weeks after exposure, nearly 10% of the inhaled fibers remained in the lung (227 +/- 103 ng/mg lung). There was evidence of a typical inflammatory response consisting of multinucleate macrophages at weeks 4 and 12, whereas immediately after the exposure, we observed numerous polymorphonuclear neutrophils. The mutant frequency significatively increased during the fourth week after the exposure: 13.5 [time] 10(-5) in the exposed group versus 6. 9 10(-5) in the control group. The induction factor, defined by the ratio of checked mutants of exposed mice to checked mutants of control mice, was 1.96. The mutation spectrum of control lung DNA and exposed lung DNA was similar, suggesting the possible involvement of a DNA repair decrease in crocidolite-treated animals. We used the (32)P-postlabeling method and did not detect any increase of either 5 mC or bulky adduct in treated mice. This is the first study that demonstrates asbestos mutagenicity in vivo after a nose-only inhalation.     

Tea as a potential chemopreventive agent in PhIP carcinogenesis: effects of green tea and black tea on PhIP-DNA adduct formation in female F-344 rats

The heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed during the cooking of proteinaceous animal foods (meat, chicken, and fish). PhIP is a carcinogen in the Fischer 344 (F-344) rat; it induces mammary tumors in female rats and lymphomas and colon and prostate tumors in male rats. In F-344 rats, PhIP forms DNA adducts in various organs, including the target organs. Inhibition of PhIP-DNA adduct formation is likely to lead to inhibition of PhIP tumorigenicity. We have examined the chemopreventive properties of green tea and black tea in PhIP carcinogenesis by evaluating their effects on PhIP-DNA adduct formation in the female F-344 rat. Young adult animals were maintained on powdered AIN-76A diet while receiving regular drinking water or 2% (wt/vol) infusions of green tea or black tea for a total of six weeks. During Weeks 3, 4, and 5, all animals received PhIP by gavage (1 mg/kg/day). Three rats per group were euthanized on Days 1 and 8 after termination of PhIP exposure. DNA was isolated from a number of organs and analyzed for PhIP-DNA adducts by 32P-postlabeling assays. Compared with animals on regular drinking water, PhIP-DNA adduct formation was inhibited in small intestine, colon, liver, and mammary epithelial cells (MECs) of animals receiving green tea or black tea as the sole source of drinking fluid. Green tea inhibited adduct formation in colon, liver, and MECs (33.3-80.0%) on both days, but only on Day 8 (54.4%) in small intestine. Black tea inhibited adduct formation on both days in liver (71.4-80.0%), on Day 1 in colon (40.0%), and on Day 8 in small intestine (81.8%); it had no effect on MEC adducts. Neither green tea nor black tea had an effect on adduct levels in pancreas, lungs, white blood cells, heart, kidneys, spleen, cecum, or stomach. Similarly, these teas did not affect the rate of adduct removal (percent change from Day 1 to Day 8) in any organ. It is concluded that green tea and black tea are potential chemopreventive agents in PhIP-induced tumorigenesis in the F-344 rat.     

硒对苯并[a]芘诱导的小鼠肺细胞DNA损伤的作用

目的　研究亚硒酸钠对苯并 [a]芘 (BaP)诱导的小鼠肺细胞DNA损伤的影响。方法　选用雄性昆明种小鼠。亚硒酸钠采用腹腔注射处理 ,BaP灌胃染毒。BaP单独作用的剂量是 12 5、2 5 0、5 0 0mg/kg;硒和BaP联合作用组采用 0 .75、1.5 0、3.0 0mg/kg的亚硒酸钠分别与 2 5 0mg/kgBaP联合染毒。设立溶剂对照组。用单细胞凝胶电泳方法检测DNA损伤的情况。结果　 12 5、2 5 0、5 0 0mg/kgBaP组小鼠肺细胞DNA损伤程度较对照组严重 ,差异有显著性 (P <0 .0 1) ,总损伤细胞百分率分别为4 3.5 0 %、84 .0 0 %、95 .6 3% ,较对照组 (9.75 % )明显增高 ,差异亦有显著性 (P <0 .0 1) ,且存在着明显的剂量 -反应关系。 0 .75、1.5 0、3.0 0mg/kg的亚硒酸钠对 2 5 0mg/kgBaP诱导的小鼠肺细胞DNA损伤具有明显的拮抗效应 ,1.5 0mg/kg亚硒酸钠的拮抗作用优于 0 .75、3.0 0mg/kg的亚硒酸钠 ,差异有显著性 (P <0 .0 5 )。结论　 12 5～ 5 0 0mg/kg的BaP可以引起小鼠肺细胞DNA损伤 ,而 0 .75～ 3.0 0mg/kg的亚硒酸钠对 2 5 0mg/kgBaP诱导的小鼠肺细胞DNA损伤具有明显的拮抗作用。