三七花提取液对小鼠的致突变作用研究

目的： 研究三七花提取液对小鼠的致突变作用。方法：分别以不同剂量(10 000、5 000、2 500 mg/kg)的三七花提取液经口灌胃染毒小鼠,每日1次,连续2 d,于第2次染毒6 h后处死小鼠,检测骨髓嗜多染红细胞微核率。另按上述剂量和分组经口灌胃连续染毒小鼠5 d,于首次染毒后第35天处死,观察精子畸形率。两项实验同时设阴性对照组(纯水)和阳性对照组(环磷酰胺,40 mg/kg)。结果：与阴性对照组比较,三七花提取液各剂量组均无致小鼠骨髓嗜多染红细胞微核作用和精子畸形作用。结论：在本实验条件下,三七花提取液对小鼠无致突变作用。     

蕨菜黄酮提取物的急性毒性和致突变性

背景与目的:研究蕨菜黄酮提取物的急性毒性与潜在致突变性.材料与方法:采用小鼠经口急性毒性试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验.结果:蕨菜黄酮提取物小鼠经口的LD50＞20.0 g/kg,小鼠骨髓细胞微核试验以及精子畸形试验结果均为阴性(P＞0.05).结论:本实验条件下,蕨菜黄酮提取物的经口LD50＞20.0 g/kg,属无毒级,未见有致突变作用.     

Tumor Induction in Monkeys after Administration of Dimethylhydrazine

1,2-Dimethylhydrazine (DMH) was administered subcutaneously to nine Macaca fascicularis monkeys (6 males and 3 females) at doses of 16 mg/kg body weight, three times a month for two years. Colon cancer was detected in two male monkeys after total DMH doses of 1080 and 3696 mg (528 and 400 mg/kg body wt., respectively). A uterine tumor was induced in one female monkey which received 3648 mg of DMH (608 mg/kg body wt.). Latent periods of tumor development were 34, 47 and 55 weeks, respectively. Histologically, the colon tumors had the structure of adenocarcinoma in both cases and the uterine tumor was diagnosed as flbromyoma.     

Tumor induction in monkeys after administration of dimethylhydrazine.

1,2-Dimethylhydrazine (DMH) was administered subcutaneously to nine Macaca fascicularis monkeys (6 males and 3 females) at doses of 16 mg/kg body weight, three times a month for two years. Colon cancer was detected in two male monkeys after total DMH doses of 1080 and 3696 mg (528 and 400 mg/kg body wt., respectively). A uterine tumor was induced in one female monkey which received 3648 mg of DMH (608 mg/kg body wt.). Latent periods of tumor development were 34, 47 and 55 weeks, respectively. Histologically, the colon tumors had the structure of adenocarcinoma in both cases and the uterine tumor was diagnosed as fibromyoma.     

奇亚籽急性毒性及遗传毒性研究

目的： 了解奇亚籽的毒理学安全性。方法：采用小鼠急性毒性试验和遗传毒性试验(Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验)对奇亚籽进行研究,小鼠急性经口毒性试验剂量为22.5 g/kg,观察经口给予受试物后14 d内动物的死亡情况;Ames试验设5个剂量,分别为每皿0.008、0.04、0.20、1.0和5.0 mg (每皿给受试物体积为0.1mL),同时设自发回变、溶剂对照(丙酮)和阳性对照(9-芴酮、2-AF、NaN3、MMC、1.8-二羟蒽锟),接种后,在37 ℃下培养48 h,计数每皿回变菌落数;小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验均设3个剂量组,分别为1.875、3.750和7.500 g/kg,同时设溶剂对照组(玉米油)和阳性对照组(环磷酰胺,50 mg/kg),分别观察骨髓涂片中嗜多染红细胞中的微核发生率和精子标本中精子畸形的类型和相应的数量。结果：奇亚籽的小鼠经口最大耐受剂量(maximum tolerated dose,MTD)>22.5 g/kg,为无毒级物质;在Ames试验、小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验中结果均呈阴性;结论：奇亚籽属于无毒级物质,亦不具有遗传毒性。     

The food-mutagens 2-amino-1-methyl-6-phenylimidazo-[4,5-b]-pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) initiate enzyme-altered hepatic foci in the resistant hepatocyte model

The initiating activity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and a mutagenic meat extract obtained from cooked meat was examined, using the resistant hepatocyte model (RH-model). Male Wistar rats were given a single i.p. injection of PhIP (50 or 75 mg/kg body weight) or MeIQx (50 mg/kg body weight) after a 2/3 partial hepatectomy (PH). The meat extract (corresponding to 1050 g meat/animal) was given by gastric feeding at three time points after PH. Two weeks after initiation the rats received a diet containing 0.02% 2-acetylaminofluorene for a period of 2 weeks. In the middle of this period a single dose of carbon tetrachloride was given. Rats were killed 6 weeks after the experimental start. The number of enzyme-altered (gamma-glutamyl-transferase positive) hepatic foci was significantly increased in the animals given MeIQx (P less than 0.05) and the highest dose of PhIP (P less than 0.01) whereas no effect of the meat extract was observed. The mutagenic meat extract was also studied with regard to promotive capacity in vivo, the meat extract was given in the diet of diethylnitrosamine initiated rats for a period of 6 weeks. No significant changes were detected after administration of the meat extract in the diet. It is concluded that both MeIQx and PhIP are weak initiators in the RH-model, in the same order of magnitude as the previously investigated, structurally related pyrolysis products. The meat extract was not active in the RH-model under the conditions used in this study.     

黑果腺肋花楸提取物的急性毒性和致突变性研究

目的：检测黑果腺肋花楸提取物的急性毒性和潜在的致突变性。方法：小鼠按20 g/kg灌胃给予黑果腺肋花楸提取物溶液，检测其急性经口毒性；采用细菌回复突变试验、小鼠骨髓细胞微核试验和精子畸形试验检测其致突变性。结果：在给予20 g/kg的黑果腺肋花楸提取物（原花青素的浓度为558 mg/kg）后，小鼠未出现中毒体征和死亡；在加与不加S9混合液的条件下，8、40、200、1 000、5 000 μg/皿5个浓度组的4种菌株的回复突变菌落数与自发回复突变菌落数相近，MR值均小于2；2.5、5、10 g/kg 3个浓度组的微核率和精子畸形率与阴性对照组的差异均无统计学意义（P > 0.05）。结论：在本实验条件下，未发现黑果腺肋花楸提取物对实验动物有急性经口毒性和致突变作用。     

黑果腺肋花楸提取物的急性毒性和致突变性研究

目的：检测黑果腺肋花楸提取物的急性毒性和潜在的致突变性。方法：小鼠按20 g/kg灌胃给予黑果腺肋花楸提取物溶液,检测其急性经口毒性;采用细菌回复突变试验、小鼠骨髓细胞微核试验和精子畸形试验检测其致突变性。结果：在给予20 g/kg的黑果腺肋花楸提取物（原花青素的浓度为558 mg/kg）后,小鼠未出现中毒体征和死亡;在加与不加S9混合液的条件下,8、40、200、1 000、5 000 μg/皿5个浓度组的4种菌株的回复突变菌落数与自发回复突变菌落数相近,MR值均小于2;2.5、5、10 g/kg 3个浓度组的微核率和精子畸形率与阴性对照组的差异均无统计学意义（P > 0.05）。结论：在本实验条件下,未发现黑果腺肋花楸提取物对实验动物有急性经口毒性和致突变作用。     

Dose-dependent promoting activity of chloroform in rat liver foci bioassay

Chloroform enhances dose-dependently the number of preneoplastic foci in livers of weanling female Sprague-Dawley rats. The preneoplastic foci were induced with a single dose of 8 mg diethylnitrosamine (DEN)/kg body wt. Thereafter chloroform was applied twice weekly for 11 consecutive weeks in doses of 100, 200 and 400 mg/kg body wt, respectively. This treatment raised the number of adenosine-5'-triphosphatase (ATPase)-deficient foci up to 5-fold, that of gamma-glutamyltranspeptidase (GGTase) and glycogen-positive foci 13- and 10-fold, respectively, after 12 weeks; 25 mg caused no effect compared to DEN-treated controls. In contrast, daily doses of chloroform only, 200 and 400 mg/kg body wt for 33 days, and 800 mg/kg body wt for 20 days given to 3-4-week-old female Sprague-Dawley rats did not lead to island formation, measured after 12 weeks, indicating a promoting rather than an initiating potency.     

Study of postnatal effects of chemopreventive agents on offspring of ethylnitrosourea-induced transplacental carcinogenesis in rats. I. Influence of retinol acetate, alpha-tocopherol acetate, thiamine chloride, sodium selenite, and alpha-difluoromethylornithine.

We studied the influence of the vitamins retinol acetate, alpha-tocopherol acetate and thiamine chloride; the antioxidant sodium selenite and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine, on the offspring of transplacental carcinogenesis by ethylnitrosourea in rats. Ethylnitrosourea was given to pregnant rats as a single i.v. injection, at a dose of 75 mg/kg body wt. or 5.5 mg/kg body wt., on the 21st day after conception. Retinol, tocopherol or thiamine was added to the diet, and selenite and alpha-difluoromethylornithine to drinking water of the offspring throughout their postnatal life at moderate doses. In control groups, ethylnitrosourea induced tumors of brain, spinal cord, peripheral nervous system and kidneys in the offspring. alpha-Difluoromethylornithine exerted a slight inhibitory effect; this agent decreased the total tumor multiplicity and the multiplicity of peripheral nervous system tumors and also prolonged survival time. Retinol, tocopherol, thiamine and selenite did not influence the development of the transplacentally-induced tumors.     

Chemopreventive effects of the aromatase inhibitor vorozole (R 83842) in the methylnitrosourea-induced mammary cancer model

The chemopreventive activity of the highly specific nonsteroidal aromatase inhibitor, vorozole, was examined in the methylnitrosourea (MNU)-induced rat model of mammary carcinogenesis. Various doses of vorozole (0.08-1.25 mg/kg body wt/day) were administered daily (by gavage) to female Sprague-Dawley rats starting at 43 days of age. Seven days later, the rats were given a single i.v. dose of MNU (50 mg/kg body wt). Rats were continually treated with vorozole until the end of the experiment (120 days post-MNU). Vorozole caused a dose dependent inhibition of mammary cancer multiplicity. The highest dose of vorozole (1.25 mg/kg body wt/day) decreased cancer multiplicity by approximately 90%, and simultaneously decreased cancer incidence from 100 to 44%. The next two highest doses of vorozole (0.63 and 0.31 mg/kg body wt/day) inhibited MNU-induced mammary cancer multiplicity by 70-80%. Even the two lowest doses of vorozole (0.16 and 0.08 mg/kg body wt/ day) decreased cancer multiplicity -50%. Serum level determinations were performed on a variety of endpoints at either 4 or 24 h following the last dose of vorozole. Insulin-like growth factor (IGF)-1 levels were slightly, but significantly, increased by vorozole treatment. Vorozole induced striking increases in serum testosterone levels at 4 h at all the dose levels employed. Testosterone levels were significantly elevated over controls at 24 h in rats given the lower doses of vorozole (0.08-0.31 mg/kg body wt/day), but were significantly lower than in rats administered the higher doses of vorozole (0.63 or 1.25 mg/kg body wt/ day). This result presumably reflects the limited half- life of vorozole in rats. In a second series of experiments, the effects of limited duration of dosing with vorozole (2.5 mg/kg body wt/day) or intermittent dosing with vorozole were determined. Treatment of rats with vorozole for limited time periods, from 3 days post-MNU administration until 30 or 60 days post-MNU treatment, resulted in significant delays in the time to appearance of palpable cancers. However, these limited treatments did not greatly affect the overall incidence or multiplicity of mammary cancers when compared with the MNU controls at the end of the study (150 days post-MNU). Finally, the effects of intermittent dosing with vorozole (2.5 mg/kg body wt/day) were examined. Rats were administered cycles of vorozole daily for a period of 3 weeks followed by treatment with the vorozole vehicle for the next 3 weeks (total of four cycles). Although this intermittent treatment did inhibit the appearance of new tumors during each of the periods that vorozole was administered, it did not cause regression of palpable cancers.      

白藜芦醇对小鼠的急性经口毒性和遗传毒性试验研究

目的：了解白藜芦醇的急性经口毒性和遗传毒性,为白藜芦醇的食用、药用安全性评价提供实验依据。方法：按照《GB 15193-2003食品安全性毒理学评价程序和方法》的规定,对白藜芦醇进行急性经口毒性测定,并通过Ames试验（每皿分别加入5000、1000、200、40、8μg白藜芦醇）、小鼠骨髓嗜多染红细胞微核试验及小鼠精子畸形试验（分别以7.500、3.750、1.875g/kg剂量的白藜芦醇给小鼠灌胃）对其遗传毒性进行评价。结果：白藜芦醇的急性经口最大耐受剂量〉15.0g/kg;3项遗传毒性试验结果均为阴性。结论：在本实验条件下,白藜芦醇对小鼠的急性经口毒性属无毒,未见遗传毒性作用。     

Effect of 'Pan Masala' on the germ cells of male mice

Cytogenetic analyses of meiotic metaphase I germ cells and abnormalities of head morphology of caudal sperms were conducted in male mice following oral feeding of Pan Masala. The substance was ground to a fine powder, dispersed in polysorbate solution and administered via gavage to the animals at 84, 420 and 840 mg/kg body weight at the rate of 10 ml/kg body weight. Polysorbate and cyclophosphamide served as the vehicle control and positive control respectively. The two higher doses, 420 and 840 mg, gave a significant increase in the frequency of X-Y univalents and breaks over those of the vehicle control. Frequency of sperm head abnormalities were significantly high for all the doses tested. The results indicate that Pan Masala is a potent clastogen, reaches the testes and affects the germinal cells.     

菁染料五甲川菁的遗传毒性研究

目的： 研究菁染料五甲川菁(Cy5)的遗传毒性,为其安全利用提供科学依据。方法：选用小鼠50只,随机分为阴性对照组(生理盐水)、阳性对照组(环磷酰胺,CP)和Cy5不同剂量试验组(2、20、200 mg/kg)。采用小鼠骨髓细胞微核试验、小鼠精子畸形试验、小鼠骨髓染色体畸变试验和Ames试验,检测Cy5的遗传毒性作用。结果：在小鼠骨髓细胞微核试验、小鼠精子畸形试验和小鼠骨髓染色体畸变试验中,Cy5各试验组与阴性对照组相比以及各试验组两两之间比较差异均无统计学意义(P均＞0.05),而各试验阳性对照组与阴性对照组相比差异均有统计学意义(P＜0.05);Ames试验结果亦呈阴性反应。结论：在本试验条件下,未观察到Cy5对小鼠的遗传毒性作用。     

Effect of dietary sodium ascorbate on 1,2-dimethylhydrazine- or methylnitrosourea-induced colon carcinogenesis in rats

The effect of dietary sodium ascorbate (SA) on colon carcinogenesisevoked by 1,2-dimethylhydrazine (DMH) or N-methyl-N-nitrosourea(MNU) was studied in female F344 rats. Animals were fed dietscontaining 0, 0.25 and 1% of SA and given s.c. a single doseof 150 mg DMH/kg body wt., 10 weekly s.c. injections of 20 mgDMH/kg body wt. or intrarectal administration of 2 mg MNU, twicea week for 2 weeks. The incidence of colon and kidney tumorswas lower in rats fed the 0.25 or 1% SA and treated with a singledose of DMH than in the animals fed the diet without SA; however,the tumor incidences did not differ between the SA- and controldiet-fed animals and treated with multiple doses of DMH or MNU.     

Chemomodulatory Action of Brassica Compestris (Var Sarason) On Hepatic Carcinogen Metabolizing Enzymes,Antioxidant Profiles and Lipid Peroxidation

The effect of two different doses (400 and 800 mg/kg body wt/day for 15 days) of a 95% ethanolic extract of the ‍seeds of Brassica compestris (var sarason) was examined on carcinogen metabolizing phase-I and phase-II enzymes, ‍antioxidant enzymes and glutathione content and lipid peroxidation in the liver of Swiss albino mice. Positive ‍control mice were treated with butylated hydroxyanisole (BHA). Significant elevation in the levels of cytochrome ‍p450 (p<0.05), cytochrome b5 (p < 0.05) glutathione s-transferase (p<0.01), DT-diaphorase (p<0.05), superoxide ‍dismutase (p<0.01), catalase (p < 0.001) and reduced glutathione (p<0.001) was noted in the group treated with 800 ‍mg/kg body wt. of Brassica extract in comparison with the negative control group. Brassica compestris acted as a ‍bifunctional inducer since it induced both phase - I and phase - II enzyme systems. Since phase-I and phase-II ‍enzymes are considered to be reliable markers for evaluating the chemoprevention efficacy of particular test materials, ‍these findings are suggestive of potential chemopreventive roles for Brassica seed extract.     

马尾松松针粉袋泡茶水提物的急性毒性和致突变性研究

目的:研究马尾松松针粉袋泡茶水提物的急性毒性和致突变性。方法:采用大、小鼠急性毒性试验,Ames试验,小鼠骨髓嗜多染红细胞微核试验和小鼠精子畸形试验对马尾松松针粉袋泡茶水提物进行急性毒性和致突变性研究。结果:马尾松松针粉袋泡茶水提物对大、小鼠经口最大耐受量(maxinally tolerated dose,MTD)均大于240.0 g/kg;Ames试验显示,在加与不加S9时各剂量组回变菌落数与自发回变对照组比较差异均无统计学意义(P0.05);小鼠骨髓嗜多染红细胞微核试验和精子畸形试验结果显示,各剂量组的微核率和精子畸形率与阴性对照组比较差异均无统计学意义(P0.05)。结论:在本次实验条件下,马尾松松针粉袋泡茶水提物经口MTD240.0 g/kg,属实际无毒级,未见致突变作用。     

Low levels of chromosomal mutations in germ cells derived from doxorubicin-treated stem spermatogonia in the mouse

The mutagenic effects of doxorubicin (Adriamycin, ADR) on mouse spermatogonial stem cells were examined by analysis of spermatocyte chromosomes and of dominant lethality transmitted through the spermatozoa. The effects of ADR on mutations, cytotoxicity, and sperm head abnormalities were compared with those of radiation. The cytotoxic effect of 6 Gy of gamma-radiation on stem spermatogonia was equivalent to about 4-5 mg ADR/kg. Chromosomal translocations were observed in 0.6% of the spermatocytes of mice treated with ADR (2-6 mg/kg). In contrast, 6 Gy of radiation induced translocations in 11.1% of spermatocytes. No increase in dominant lethality was observed after treatment with ADR at doses up to 6 mg/kg, while the frequency after 6 Gy of radiation was 3.6%. Based on these results, ADR would be expected to be only a weak inducer of balanced chromosomal rearrangements. Because ADR at 4.5 mg/kg was much weaker than 6 Gy of gamma-radiation at inducing chromosomal translocations, but just as effective at inducing sperm head abnormalities, the level of sperm head abnormalities is not indicative of balanced chromosomal rearrangements induced in stem spermatogonia by cytotoxic agents.     

两种新型杀虫剂对蚯蚓精子形态的影响

本文提出了一种检测及评价土壤生态系统中遗传毒性的新方法。赤子爱胜蚓（Ｅｉｓｅｎｉａ ｆｏｅｔｉｄａ）经人工土壤法污染毒,暴露于不同剂量的两种新型杀虫剂－吡虫啉和抑食肼中,观察它们对蚯蚓精子形态的影响。实验结果表明,吡虫啉在浓度大于０．５ｍｇ／ｋｇ干土对蚯蚓精子畸变率有明显影响（Ｐ〈０．０１）,并呈现剂量效应关系;而抑食肼在浓度高达１００ｍｇ／ｋｇ干土时,与对照组相比才有显著差异（Ｐ〈０．０５）．     

Effect of streptozotocin diabetes on development of nitrosamine-induced pancreatic carcinoma when diabetes induction occurs after nitrosamine exposure

Diabetes mellitus has been suggested as a possible risk factorfor the development of pancreatic cancer in humans. Previousstudies in our laboratory have shown, however, that streptozotocin(STZ) diabetes inhibits the development of cancer of the exocrinepancreas in hamsters when STZ is administered prior to treatmentwith the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine(BOP). It has been reported by others that the concurrent administrationof BOP and STZ enhances pancreatic carcinogenesis in hamsters.The purpose of the present study was to determine the effectof STZ diabetes on the development of BOP-induced pancreaticcarcinoma when STZ is given following exposure to BOP. Groupsof Syrian golden hamsters were treated with either BOP only(single s.c. injection, 40 mg/kg body wt at week 0), BOP (singles.c. injection, 40 mg/kg body wt at week 0) plus STZ (50 mg/kgbody wt x3 daily i.p. doses at weeks 10, 20 or 30), STZ only(50 mg/kg body wt x3 daily i.p. doses at weeks 10, 20 or 30),or neither BOP nor STZ. The experiment was terminated at 40weeks after BOP treatment. No significant difference was seenin the incidence of pancreatic cancer between those animalsreceiving BOP only at week 0 and those receiving BOP at week0 plus STZ at weeks 10, 20 or 30 of the study. The results wouldappear to indicate that STZ diabetes, established after BOPtumor initiation, plays no apparent role in the modulation ofpancreatic carcinogenesis.