罗汉果对雄性小鼠骨髓微核和精子形态的影响

背景：对罗汉果的遗传毒性进行研究,可为其安全使用提供实验依据。 目的：观察罗汉果水提液对雄性小鼠骨髓细胞微核率和附睾精子畸形率的影响,了解其是否有遗传毒性。 方法：按罗汉果水提液最大使用剂量(3 g/mL)和最大灌胃容量(20 mL/kg)灌胃小鼠,观察罗汉果水提液的急性毒性。将雄性昆明小鼠随机分为5组,分别灌胃给予30,15,7.5 g/kg的罗汉果水煎液、蒸馏水,连续5 d;或腹腔注射40 mg/kg环磷酰胺。于灌胃第5天,采用骨髓嗜多染红细胞微核试验计算小鼠的骨髓微核率。于首次灌胃后第35天,观察小鼠精子畸形率。 结果与结论：罗汉果水提液对昆明小鼠的经口急性毒性最大耐受剂量大于120 g/kg。罗汉果水提液30,15,7.5 g/kg灌胃后,小鼠的骨髓微核率、精子畸形率与正常小鼠无差异(P > 0.05),均明显低于环磷酰胺诱发的骨髓微核率和精子畸形率(P < 0.05)。说明罗汉果水提液对成年雄性小鼠无明显遗传毒性。     

氟西汀对雄性小鼠的遗传毒性研究

目的探讨氟西汀对成年雄性小鼠的遗传毒性。方法采用小鼠急毒试验、小鼠精子畸形试验、小鼠骨髓微核试验及生殖、淋巴器官重量指数分析方法。结果氟西汀对小鼠经1：2最大耐受剂量为15g／kg微核试验与精子畸形试验的小鼠均分6组,即氟西汀1.25mg／kg,2.5mg／kg,5mg／kg和10mg／kg4个剂量组与阴、阳性对照组其中灌胃剂量为1.25mg／kg、2.5mg／kg、5mg／kg时,均未诱发各组的精子畸形率、骨髓微核率增高,与阴性对照组相比均无显著差异（P〉0.05）;当剂量达到10g／kg时诱发的精子畸形率、骨髓微核率均略高于阴性对照组但有显著性差异（P〈O.05）;灌胃氟西汀各剂量组小鼠的生殖与淋巴器官重量指数与阴性对照组相比无显著变化（P＞O.05）。结论经口最大给药剂量为15g／kg,属于无毒级。氟西汀以1.25mg／kg、2.5mg／kg、5mg／kg的剂量灌胃小鼠无生殖与遗传毒性,当灌胃剂量达到30g／kg时,则对雄性小鼠有轻微的潜在遗传毒性。     

罗汉果甜甙对雄性小鼠的遗传毒性研究

目的探讨罗汉果甜甙对成年雄性小鼠的遗传毒性。方法采用小鼠急毒试验、小鼠精子畸形试验、小鼠骨髓微核试验及生殖、淋巴器官重量指数分析方法。结果罗汉果甜甙对小鼠经口最大耐受剂量为15异／kg。微核试验与精子畸形试验的小鼠均分6组，即罗汉果甜甙0．25g／kg、0．5g,／kg、1g/kg、5g／kg4个剂量组与阴、阳性对照组。其中灌胃剂量为0．25g/kg、0．5g／kg、1g／k时，均来诱发各组的精子畸形率、骨髓微核率增高，与阴性对照组相比均无显著差异（P〉0．05）：当剂量达到5g／kg时诱发的精子畸形率、骨髓微核率均略高于阴性对照组但有显著性差异（P〈0．05）。灌胃罗汉果甜甙各剂量组小鼠的生殖与淋巴器官重量指数与阴性对照组相比无显著变化（P〉0．05）。结论经口最大给药剂量为15g／kg，属于无毒级。罗汉果甜甙以0．25g／kg，0．5g／kg及1g/kg的剂量灌胃小鼠无生殖与遗传毒性。当灌胃剂量达到5g／奴时，则对雄性小鼠有轻微的潜在遗传毒性。     

巴豆对小鼠骨髓及胚胎肝细胞微核率的影响

目的　探讨孕妇禁忌中药巴豆水提液对小鼠骨髓细胞及胚胎鼠肝细胞微核率的影响。方法　采用小鼠骨髓嗜多染红细胞微核 (MN)实验法与小鼠胚胎肝转移微核实验法。结果　当小鼠用药剂量在 1g/kg、 5g/kg时微核率与阴性对照组无明显差异 ,10g/kg时诱发骨髓MN率与阴性对照组比较有显著差异 (P <0 0 1)。而在孕鼠用药 1g/kg、 5g/kg、 10g/kg各剂量组时均可诱发鼠胎肝细胞微核率增高。各组与阴性对照组比较都有显著性差异 (P <0 0 1)。结论　实验表明巴豆水提液在同等剂量作用下诱发胚胎鼠肝细胞微核率明显高于成年鼠骨髓细胞 ,此药可以通过胎盘屏障 ,对胎鼠具有更为显著的致遗传物质损伤作用。     

桑寄生水煎液对SD孕鼠及胚胎发育的影响

目的探讨桑寄生水煎液对sD孕鼠及胚胎发育的毒性。方法选出孕第0天孕鼠60只,随机分成5组,每组12只。阴性对照组（按照1ml／100gBW剂量灌胃生理盐水）、桑寄生水煎液实验3各组（按照40g/kg、20g／b、10g／kg剂量分3组灌胃）,均于孕第6—18d,1次／日,阳性对照组（环磷酰胺,按照12．5mg／kg剂量腹腔注射）,于孕第13d腹腔注射1次。各组孕鼠均于孕18d麻醉解剖腹腔,取出卵巢、子宫、胚胎,观察胚胎外观,称胚胎重、子宫重与卵巢重,并测量胎鼠身长、尾长,每窝均取出1／2数量的胚胎制成骨骼双染标本后,在体视显微镜下：观察枕骨与胸骨发育情况、测量记录胚胎四肢主要长骨的骨化长度。结果（1）桑寄生水煎液三个剂量的实验组孕鼠在孕期体重总增重、卵巢与子宫脏器重量指数与阴性对照组比较,无显著性差异（P〉0．05）,与环磷酰胺组比较,差异有显著性（P〈0．05）;（2）桑寄生水煎液三个剂量实验组胎鼠体重、身长、尾长及畸胎率与阴性对照组相比,均无显著性差异（P〉0．05）,与环磷酰胺组比较差异有显著性（P〈0．05）。（3）桑寄生水煎液三个剂量实验组胚胎的枕骨评分、胸骨节数及四肢主要长骨的骨化点长度与阴性对照组比较,均无显著性差异（P〉0．05）,与环磷酰胺组比较差异有显著性（P〈0．05）。结论在本实验条件下,桑寄生水煎液三个剂量组对sD孕鼠无母体毒性,无致畸效应及胚胎发育毒性。     

柠檬黄对雄性小鼠生殖细胞的影响

探讨柠檬黄对雄性小鼠生殖细胞的影响.选择成年雄性小鼠分别给予柠檬黄0.25 g/kg(低剂量组)、0.5 g/kg(中剂量组)和1 g/kg(高剂量组),连续灌胃染毒5d,通过小鼠精子畸形率、精细胞微核率以及睾丸形态变化等方面来评价柠檬黄对生殖细胞的影响.与对照组相比,高剂量组的柠檬黄能引起小鼠精子的畸形率和精细胞微核...     

装潢居室空气中挥发性化学物的遗传毒性研究

目的探讨装潢居室空气中挥发性化合物的遗传毒性.方法采用小鼠骨髓嗜多染性红细胞微核试验和小鼠精子畸形试验检测居室装潢后空气中挥发性化合物的遗传毒性.结果该化合物对小鼠呼吸系统有明显的刺激作用,与阴性对照组比较,高、中、低剂量组的微核率、精子畸形率均有显著差异性.结论居室装潢后室内空气中挥发性化合物具有遗传毒性作用.     

柠檬黄对雄性小鼠生殖细胞的影响

探讨柠檬黄对雄性小鼠生殖细胞的影响。选择成年雄性小鼠分别给予柠檬黄0.25 g/kg（低剂量组）、0.5 g/kg（中剂量组）和1 g/kg（高剂量组）,连续灌胃染毒5 d,通过小鼠精子畸形率、精细胞微核率以及睾丸形态变化等方面来评价柠檬黄对生殖细胞的影响。与对照组相比,高剂量组的柠檬黄能引起小鼠精子的畸形率和精细胞微核率升高（P〈0.05）,而中、低剂量组没有明显的变化（P〉0.05）。睾丸组织切片显示,低、中剂量组与对照组相比没有明显改变,高剂量组小鼠睾丸生精小管管腔内可见精子数量减少,生精上皮细胞层次减少,部分细胞有浓缩、溶解等坏死样变。高浓度的柠檬黄能使雄性小鼠精子畸形率增加,并造成雄性小鼠精细胞微核率上升,有一定的致突变性。     

中药对小鼠骨髓细胞遗传物质影响的实验研究

目的：通过本实验研究探讨孕妇禁忌中药红花、牛膝对小鼠骨髓嗜多染红细胞微核频率的影响。方法：选用体重18－22g的雌性昆明小鼠，随机分为8组，即阴性、阳性对照组分别灌胃生理盐水及腹腔注射环磷酰胺30mg/kg；实验组用红花及牛膝水煎剂分别以10g/kg,2g/kg,1g/kg的剂量灌胃，每天1次，连续5天后断颈取骨髓细胞涂片观察。结果：各用药剂量组诱发小鼠骨髓细胞微核率虽有数目的差异，但与阴性对照组相比无显著性差异（P＞0．05），而与阳性对照组相比均有显著差异，P＜0．01。讨论：本实验结果提示孕妇禁忌中药红花、牛膝虽有影响生育的作用，但是无明显诱发小鼠骨髓微核率增高的作用，表明这两种中药均无损伤遗传物质的作用。     

甲醛与苯联合染毒对子代胎鼠遗传毒性的研究

目的研究甲醛和苯对子代胎鼠的遗传损伤作用。方法选用昆明种雌鼠44只,随机分为11组,为阴性对照组、阳性对照组（用子代胎鼠肝细胞微核检测）和9个实验组。实验组浓度甲醛剂量为（0.8mg/m^3、1.6mg/m^3、3.2mg/m^3）,苯剂量为（495mg/m^3、990mg/m^3、1980mg/m^3）,苯＋甲醛联合染毒。采用微核试验和彗星试验检测甲醛和苯的遗传毒性。结果（1）随着剂量的增加,各染毒组胎肝细胞微核率与阴性对照组比较差异有显著性（P〈0.01）,甲醛与苯联合暴露对胎肝细胞微核率具有协同作用（P〈0.05）。（2）在受试剂量范围内,小鼠胎肝细胞彗星率随苯或甲醛染毒剂量增加而增加（P〈0.01）,其彗星尾部DNA百分率（%）与尾距随苯染毒剂量增加而延长（P〈0.01）,随甲醛染毒剂量增加高剂量染毒组明显低于中剂量染毒组（P〈0.01）;联合染毒组中尾距随联合染毒中苯染毒剂量增加而延长（P〈0.01）,随联合染毒中甲醛染毒剂量增加高剂量染毒组明显低于中剂量染毒组（P〈0.01）。苯与甲醛联合作用经析因素分析存在协同作用（P〈0.01）。结论更多甲醛和苯具有明显的遗传毒性作用,能增强彼此的胎肝细胞损伤效应。     

Evaluation of the genotoxic effects of pyrimethamine, an antimalarial drug, in the in vivo mouse

Pyrimethamine is an antimalarial drug and a known teratogenic agent. With this drug, positive and negative results have been reported by various investigators in in vivo and in vitro genotoxicity/mutagenicity assays. In this investigation the genotoxic effects of pyrimethamine (PY) were tested in mice in vivo systems, using the bone marrow micronucleus test (MNT) and the transplacental MN test (TMNT). PY at the highest dose (40 mg/kg) induced statistically significant MN in bone marrow cells at 24 and 48 h. In the transplacental MN test, PY did not induce significant MN in fetal liver or in maternal bone marrow. Teratogenesis Carcinog. Mutagen. 20:65-71, 2000.     

Assessment of 1,2-dimethylhydrazine in bone marrow micronucleus assay: variations in protocol and response.

The effect of variations in experimental protocol on the assessment of the genotoxicity of 1,2-dimethylhydrazine (DMH) in the bone marrow micronucleus assay was determined. The incidence of micronuclei (MN) in the bone marrow of CBA mice treated with DMH (either intraperitoneally (i.p.) or orally) was found to be significantly greater than that observed in C57B1/6J mice using the same dose and dosing regimen. With i.p. injection, DMH, at doses of 20 and 50 mg/kg, was found to be positive in the bone marrow MN test in CBA mice only. In C57B1/6J mice, DMH (i.p.) was found to be positive at only the 50 mg/kg dose. With oral administration, DMH was positive in the MN test only at the 50 mg/kg dose and only in CBA mice. No significant difference in the percentage of MN was observed when 300, 500, or 1,000 polychromatic erythrocytes (PCEs) were scored following a single treatment of DMH. Cyclophosphamide (CY) was found to induce a dose-dependent increase in the percentage of MN observed in the bone marrow of C57B1/6J mice. DMH tested positive in the colon nuclear aberration (NA) assay in both strains of mice using both i.p. and oral routes of administration, although C57B1/6J mice were found to be more sensitive than CBA mice. No significant difference was observed regarding the percentage of NAs observed in the colon between mice injected i.p. or orally gavaged.     

Reconciliation of five negative and four positive reports of the activity of dimethylnitrosamine in the mouse bone marrow micronucleus assay

Five positive and four negative reports of the activity of dimethylnitrosamine(DMN) in the mouse bone marrow micronucleus assay exist in theliterature: toxicity and micronucleus experiments have beenconducted to resolve this finely balanced conflict of data.The maximum dose at which mice can survive a single treatmentwith DMN is 10–12.5 mg/kg. A dose of 15 mg/kg is lethalwithin 4 days while higher doses are lethal within 1–2days. None the less, micronucleus assays can be conducted withDMN up to dose levels of 100 mg/kg if animals are sampled within24 h of dosing, i.e. before they die. We have demonstrated clearpositive assay responses for DMN at lethal dose levels (30 and60 mg/kg). At non-lethal (maximum tolerated) dose-levels (10and 12.5 mg/kg) marginal positive or negative responses wereobserved. Both the oral and intraperitoneal injection routesof exposure have been studied. These observations enable thenine previous and divergent literature reports to be explained.The present data for DMN focus attention on the need to considercarefully the selection of dose-levels for use in short-termin vivo genotoxicity assays. In particular, it is suggestedthat many of the conflicts of assay data that exist in the literaturemay be caused by the failure of investigators to study, adequately,the toxicity of chemicals. It is proposed that positive genotoxicitytest data generated only at lethal dose-levels are of no toxicologicalvalue. ¹To whom correspondence should be addressed     

Coumarin inhibits micronuclei formation induced by benzo(a)pyrene in male but not female ICR mice.

Coumarin has been shown to be an effective inhibitor of carcinogenesis in rodents if given before and during the carcinogen treatment. We investigated the possibility that pretreatment with coumarin would inhibit the genotoxicity of benzo(a)pyrene (BP) in ICR mice as indicated by the bone marrow micronucleus test, a widely used in vivo test for genotoxicity. Our studies showed that pretreatment of male mice with doses of coumarin at 65 or 130 mg/kg/day for 1 week (with 1 day of no treatment at midweek) partially inhibited the genotoxicity of BP at a single intraperitoneal dose of 150 mg/kg. Time course experiments showed a decrease in induced micronuclei in the bone marrow at several time points after the BP treatment, thus indicating a true inhibition and not a lag in the induction of micronuclei. However, no inhibition in micronuclei formation was seen in female mice pretreated with the same doses of coumarin. Coumarin treatment alone did not induce micronuclei in either sex. Future studies are needed to analyze the mechanisms responsible for the difference noted between the sexes.     

Benzidine and 3,3'-dichlorobenzidine (DCB) induce micronuclei in the bone marrow and the fetal liver of mice after gavage

Single oral dose of benzidine (300 mg/kg) and DCB (1000 mg/kg)to male ICR mice elicited positive response in the bone marrowmicronucleus test. In the transplacental micronucleus test,the compounds were administered to pregnant females in the samemanner. A significant increase in the frequency of micronucleioccurred in the fetal liver, but not in the bone marrow of mothers.The relative values of bone marrow and transplacental micronucleustests for the prediction of carcinogenicity of these compoundsis discussed.     

Acute oral toxicity evaluation of biodegradable and pH-sensitive hydrogel based on polycaprolactone, poly(ethylene glycol) and methylacrylic acid (MAA)

In this article, a novel biodegradable and pH-sensitive hydrogel based on polycaprolactone, poly(ethylene glycol) and methylacrylic acid (MAA), was prepared by UV-initiated free radical polymerization. The obtained hydrogel was characterized by (1)H NMR and FTIR. The acute toxicity tests and histopathological study were performed in BALB/c mice. In acute oral toxicity test, mice were orally administered with a total 15 g/kg body weight (b.w.) of P(CL-MAA-EG) hydrogels, and were observed continuously for 14 days. For histopathologic study, samples including heart, liver, lung, kidneys, spleen, stomach, and intestine, were histochemically prepared and stained with hematoxylin-eosin for histopathologic examination. No mortality or significant signs of acute toxicity was observed during the whole observation period, and no macroscopic alteration was found in the organs. Histopathological analysis of various organs also did not show any significant pathological changes. Thus, the maximal tolerance dose of P(CL-MAA-EG) hydrogels was calculated to be higher than 15 g/kg b.w. in BALB/c mice. It was suggested that the studied P(CL-MAA-EG) hydrogel in this article were nontoxic after acute oral administration and it might be a promising candidate as a novel oral drug carrier.     

Assessment of the genotoxic potential of ISIS 2302: a phosphorothioate oligodeoxynucleotide

ISIS 2302, a phosphorothioate oligodeoxynucleotide with antisense activity against human ICAM-1 mRNA, was evaluated in a battery of tests to assess genotoxic potential. There was no evidence of genotoxicity in three in vitro studies performed: (i) a bacterial reverse mutation test; (ii) a chromosomal aberration test in Chinese hamster ovary cells; (iii) a mammalian cell gene mutation assay in L5187Y cells. Additionally, there was no in vivo evidence of genetic toxicity in a bone marrow micronucleus study in male and female mice. For all tests, top concentrations or doses assessed met harmonized regulatory guidelines. The cellular uptake of ISIS 2302 into target cells was confirmed using capillary gel electrophoresis and immunohistochemistry. Intracellular uptake into CHO cells, L5187Y cells, Salmonella typhimurium TA98 and bone marrow was concentration- and time-dependent. Consistent with what is known about the physical and chemical properties of phosphorothioate oligodeoxynucleotides, there was no evidence of genotoxicity in any of the assessed end-points. Furthermore, the absence of genotoxicity could not be ascribed to test system insensitivity or to an absence of exposure of the test system to ISIS 2302.