海狗油脂肪乳对大鼠致畸毒性研究

背景与目的:探讨海狗油脂肪乳对大鼠致畸毒性作用。材料与方法:孕鼠设3个海狗油脂肪乳剂量组(800、400和200mg/kg)、环磷酰胺(CP)阳性对照组和溶剂对照组。在受孕大鼠妊娠的第6～15d连续尾静脉注射受试物10d,阳性对照组大鼠妊娠第10d一次性腹腔注射CP。结果:与溶剂对照组比较,海狗油脂肪乳200mg/kg剂量组的孕鼠体重增长缓慢(P<0.01);400mg/kg剂量组出现胎仔身长和体重减轻的胚胎毒性(P<0.05);800mg/kg剂量组出现吸收胎数增多(P<0.05)。各剂量组胎仔的黄体数、着床数、活胎数、死胎数、胎仔尾长和胎仔性别等与溶剂对照组间的差异无统计学意义(P>0.05)。海狗油脂肪乳各剂量组未见明显的骨骼畸形和内脏器官畸形。结论:海狗油脂肪乳剂量在200mg/kg时,对大鼠具有一定的母体毒性;海狗油脂肪乳在剂量400mg/kg时有胚胎毒性;在剂量800mg/kg时,未见大鼠胎仔骨骼和内脏器官的致畸毒性。     

CCS注射液对大鼠胚胎毒性、致畸毒性的研究

CCS注射液是西药一类新药,临床用于抗肿瘤,为了考察该药有否胚胎毒性和致畸毒性,本文进行了动物致畸试验研究。采用Wistar种大白鼠,体重250－280g,每笼雄鼠1只、雌鼠2只进行交配,交配后的雌鼠合笼饲养,每组受孕鼠＞16只,试验共分3个受试药物组（200mg/kg,100mg/kg和50mg/kg),1个空白对照组和1个阳性对照组（CP10mg/kg)。在胚胎器官形成期即妊娠第6－15d连续皮下注射给药（阳性对照在妊娠第10d天一次腹腔注射给药）,在妊娠第0d,6d,10d,13d,16d,18d和20d称孕鼠体重,于妊娠第20d处死动物,剖腹取胎,计数每只孕鼠的黄体数、着床数、活胎数、死胎数（包括吸收胎、早期和晚期死胎）和胎仔性别;秤取胎仔体重;1／2胎仔检查骨骼发育情况,另1／2胎仔检查体表、内脏器官发育情况。结果显示：阳性对照组在妊娠18d后体重增长减慢,与空白对照组比较平均体重最大差值达36g,统计学分析具有显著性差异。高剂量组和阳性对照组的活胎数减少（窝平均活胎数分别为6.8和4.9个,而空白对照组为11.7个）,死胎数增加（窝平均死胎数分别为6．9和8．8个,空白对照组为0．7个）,阳性对照组还出现胎仔体重减轻（平均体重3．3g,而空白对照组为4.2g）等,具有统计学差异的数值。而该药对胎仔的性别则未见差异。胚胎骨骼检查,总畸形率空白对照组和各受试药物组均＜7．0％;而阳性对照组高达97．7％。胚胎体表和内脏器官发育检查,总畸形率空白对照组仅3．3％;各受试药物组＜9．3％;而阳性对照组高达48．4％。上述结果证实,在大鼠胚胎器官形成期连续皮下注射给予CCS注射液,在200mg/kg组存在活胎数减少和死胎数增多等异常指标;在100mg/kg和50mg/kg组未发现孕鼠体重增长缓慢和胚胎毒性。各受试药物组未明显的骨骼畸形和组织器官畸形,提示CCS注射液对大鼠存在明显胚胎毒性,但不存在致畸毒性。     

116. CCS注射液对大鼠胚胎毒性、致畸毒性的研究

CCS注射液是西药一类新药，临床用于抗肿瘤。为了考察该药有否胚胎毒性和致畸毒性，本文进行了动物致畸胎试验研究。采用Wistar种大白鼠，体重250～280 g，每笼雄鼠1只、雌鼠2只进行交配，交配后的雌鼠合笼饲养，每组受孕鼠＞16只。试验共分3个受试药物组（200 mg/kg、100 mg/kg和50 mg／kg ），1个空白对照组和1个阳性对照组（CP 10 mg／kg）。在胚胎器官形成期即妊娠第6～15 d连续皮下注射给药（阳性对照在妊娠第10 d天一次腹腔注射给药），在妊娠第0 d、6 d、10 d、13 d、16 d、18 d和20 d称孕鼠体重；于妊娠第20 d处死动物，剖腹取胎，计数每只孕鼠的黄体数、着床数、活胎数、死胎数（包括吸收胎、早期和晚期死胎）和胎仔性别；秤取胎仔体重；1/2胎仔检查骨骼发育情况，另1／2胎仔检查体表、内脏器官发育情况。结果显示：阳性对照组在妊娠18 d后体重增长减慢，与空白对照组比较平均体重最大差值达36 g，统计学分析具有显著性差异。高剂量组和阳性对照组的活胎数减少（窝平均活胎数分别为6．8和4．9个，而空白对照组为11．7个），死胎数增加（窝平均死胎数分别为6．9和8．8个，而空白对照组为0．7个）；阳性对照组还出现胎仔体重减轻（平均体重3．3g，而空白对照组为4．2g）等，具有统计学差异的数值。而该药对胎仔的性别则未见差异。胚胎骨骼检查，总畸形率空白对照组和各受试药物组均＜7．0%；而阳性对照组高达97．7%。胚胎体表和内脏器官发育检查，总畸形率空白对照组仅3．3%；各受试药物组＜9．3%；而阳性对照组高达48．4％。上述结果证实，在大鼠胚胎器官形成期连续皮下注射给予CCS注射液，在200 mg/kg组存在活胎数减少和死胎数增多等异常指标；在100 mg/kg和50 mg/kg组未发现孕鼠体重增长缓慢和胚胎毒性。各受试药物组均未见明显的骨骼畸形和组织器官畸形。提示CCS注射液对大鼠存在明显胚胎毒性，但不存在致畸毒性。     

117. 新药轻灵-盐酸西部曲明的致畸敏感期毒性研究

目的：为评价新药轻灵-盐酸西布曲明（Qingling-Sibutramine hydrochloride,简称Ql-Sibutramine）的生殖毒性,对其进行了二阶段经典致畸试验。方法：根据我国卫生部药政局《新药临床前毒理学研究指导原则》进行本试验。将交配获得的孕大鼠按受孕时间先后,随机分为5组,设0.5 mg／kg,3.16 mg／kg和20 mg／kg受试物3个剂量组,另设阴性对照（蒸馏水）和阳性对照（敌枯双1 mg／kg）,每组20只。各组孕鼠均于孕期第20日称重后处死,剖腹摘出子宫称重并检查记录每窝的着床数、吸收胎数、死胎数、活胎数并计数两侧卵巢表面黄体数。称量活胎仔体重及测量身长,并检查活胎的外观畸形、内脏畸形和骨骼畸形。结果及结论：①溶剂对照物（蒸馏水）对孕母鼠（P）和胎鼠（F1）各项毒效应观察指标均无影响,而阳性对照物（敌枯松）不但对孕母鼠有母体毒性（体重,窝重和活胎鼠数降低,死胎数增加）,而且对胎鼠有明显致畸性效应（外观畸形率、内脏畸形率和骨骼畸形率分别为65.3％、85.3％和37.5％）,表明本实验系统可靠。②3个受试药物（Ql-Sibutramine）剂量组不影响交配雌鼠的受孕能力,但中高剂量组孕大鼠呈现不同程度母体毒性反应,表现为摄食量减少和体重增长缓慢;③受试药物（Ql-Sibutramine）不影响交配鼠受精卵着床和着床后胚胎存活;④3个Ql-Sibutramine剂量组未诱发胎鼠（Fl）出现外观、内脏和骨骼的致畸效应。但中高剂量组胎鼠存在不同程度发育毒性,主要为平均体重和身长降低,起因于孕母鼠摄食量减少,从而也导致胎鼠（子代）平均体重和身长降低,表现一定的发育毒性。     

Teratogenesis study of sodium lactate in rats

目的:检测乳酸钠对大鼠是否存在胚胎毒性和致畸毒性.方法:采用SD孕鼠,每组孕鼠＞12只.试验分为乳酸钠3个剂量组(750、1 500和3 000 mg/kg),阳性对照组(10 mg/kg环磷酰胺)和溶剂对照组(双蒸水),在胚胎器官形成期连续经口灌胃给予乳酸钠10d,妊娠第20 d处死动物.剖腹取胎,检测乳酸钠对大鼠的母体毒性和胚胎毒性,并观察胎仔骨骼发育和内脏器官发育情况.结果:与溶剂对照组比较,阳性对照组出现活胎数减少、死胎及吸收胎数增多,胎仔身长、尾长、体质量减少,骨骼和内脏器官发育不全和畸形率升高等异常(P＜0.05).除乳酸钠1 500和3 000 mg/kg组在妊娠后期孕鼠体质量增长减慢,出现母体毒性外,其他各项指标,即黄体、着床、活胎、死胎和吸收胎的计数,子宫及胎仔的质量,身长和尾长的测量,内脏器官发育不全和畸形率,骨骼的骨化不全和畸形率等与溶剂对照组基本一致,均未见明显异常(P＞0.05).结论:乳酸钠在＞1 500 mg/kg剂量时,对大鼠具有母体毒性,未见胚胎毒性和胎仔骨骼、内脏器官的致畸毒性.     

海狗油脂肪乳的致突变试验研究

目的 目的观察海狗油脂肪乳是否存在遗传毒性.方法 应用Ames试验、中国仓鼠肺细胞体外培养染色体畸变试验和小鼠骨髓嗜多染红细胞微核试验,研究海狗油脂肪乳的致突变作用.结果 Ames试验在P《5.0mg/皿浓度下未见回复突变菌落数显著增加;中国仓鼠肺细胞体外培养染色体畸变试验在P《6.6mg/ml浓度下未出现细胞染色体畸变率显著增高;小鼠骨髓嗜多染红细胞微核试验在P《6.0g/kg剂量下未诱发微核细胞率的增高.结论 海狗油脂肪乳在试验剂量范围内,无致突变作用.     

司丙红毒素对大鼠致畸性研究

背景与目的观察司丙红霉素对大鼠的致畸毒性。材料与方法应用SD大鼠进行致畸毒性研究,以75,200和400mg/kg3个剂量组给药,并设阴性对照组(0.5%羧甲基纤维素纳)及阳性对照组(水杨酸钠)给药时间为大鼠妊娠后第6~15d。结果200和400mg/kg组妊娠大鼠在给药后出现厌食、活动减少,对妊娠大鼠各期体重增长值进行t检验,显示200、400mg/kg组大鼠妊娠10~13d时体重增长值明显低于阴性对照组,停药后体重增长正常;各剂量组妊娠大鼠生育能力与阴性对照组比较无差异;各剂量组与阴性对照组胎仔的外观未见畸形,胎仔的身长、尾长经t检验,差异无统计学意义。胎仔骨骼、内脏发育未见异常。结论中、高剂量组对妊娠大鼠有母体毒性,表现为体重下降、厌食,但无胚胎毒和致畸作用。     

富硒大蒜对大鼠的胚胎毒性和致畸毒性研究

目的 通过在胚胎器官形成期连续给药,观察富硒大蒜对大鼠是否存在胚胎毒性和致畸毒性.方法 采用 Wistar大鼠,每组妊娠鼠＞15只.试验设3.50 g/kgbw、1.75 g/kgbw和0.88 g/kgbw 3个剂量组,同时设1个阳性对照组和1个溶剂对照组.在大鼠胚胎器官形成期连续灌胃给药10 d(孕6-15 d),在妊娠的第20 d,处死妊娠鼠,计数黄体数、胚胎的着床数、活胎数、早期死胎数(包括吸收胎)和晚期死胎数.观察胎仔性别、外观并称取体重后,将每窝1/2的活胎仔乙醇固定,2﹪氢氧化钾软化,茜素红染色,甘油透明后在大视场工作仪上检查骨骼发育情况.另1/2活胎仔经Bouins液固定后,在大视场工作仪上检查内脏发育情况.结果 受试药物各剂量组均未显示出明显的胎仔生长发育障碍及骨骼和内脏畸形.结论 富硒大蒜在＜3.5 g/kg剂量,对大鼠不具有母体毒性和胚胎毒性,未见胎仔骨骼和内脏器官的致畸毒性.     

青蒿素哌喹复方对大鼠致畸敏感期毒性试验

背景与目的:青蒿素哌喹复方(artemisinin-pipemquine combination,ATQ)是由青蒿素与哌喹组成的抗疟复方,本研究观察其对大鼠母体及胎仔的影响.材料与方法:将SD孕鼠随机分为6组,每组18只.设ATQ 35、70、120、200 ms/(ks·d)4个剂量组,另设溶剂对照和环磷酰胺阳性药物对照组.大鼠妊娠7～17d每天灌胃ATQ 1次,妊娠20 d处死,检查各项指标.结果:ATQ70 mg/(ks·d)及以上剂量延缓大鼠胎仔发育,胎仔体重及身长低于溶剂对照组(P0＜0.01);ATQ 120 ms/(ks·d)和200 mg/(ks·d)剂量对大鼠胎仔有致死毒性,胚胎着床后损失率分别为25.5%和38.8%,高于溶剂对照组(P＜0.01);ATQ 120 mg/(ks·d)和200 mg/(ks·d)剂量组出现胎仔骨骼畸形,主要表现为肋骨隆突、缺失、骨化不全及短多肋(14肋)等;ATQ 35 mg/(ks·d)剂量对母鼠及胎仔发育未表现出毒性.结论:ATQ对SD大鼠具有发育毒性;在本实验条件下,35 mg/(ks·d)剂量为孕鼠的最大安全剂量.     

玉米赤霉醇对大鼠的胚胎毒性

背景与目的：观察玉米赤霉醇（α- zearalanol,Zeranol）对大鼠的胚胎毒性作用。材料与方法：将交配成功的Wistar大鼠随机分成溶剂对照组(阴性对照)、阳性对照组（乙酰水杨酸）和实验组（Zeranol 1、10、100 mg/kg 3个剂量组）,实验组大鼠于妊娠7~16 d灌胃染毒,各组大鼠均于妊娠20 d处死。剖腹取子宫称重,记录活胎、死胎、吸收胎数,测量胎仔发育指标并检查其畸形。结果：高剂量组孕鼠全部流产;中剂量组孕鼠的增重明显低于阴性对照组,差异有统计学意义(P＝0.000),且活胎减少,死胎和吸收胎增加(P＝0.000),胎仔平均体重、身长、尾长明显低于阴性对照组,差异有统计学意义(P＝0.000);小剂量组与阴性对照组相比差异无统计学意义。中、低剂量组胎鼠的外观、内脏和骨骼均未见明显畸形。结论：在本试验条件下,10 mg/kg以上剂量的Zeranol对大鼠有胚胎毒性作用。     

Carcinogenesis Studies of Dichlorvos in Fischer Rats and B6C3F1 Mice

Dichlorvos (dichlorovinyl dimethyl phosphoric acid ester) is a cholinesterase inhibitor used widely as a contact and stomach insecticide for control of internal and external parasites. Carcinogenesis studies were conducted by administering dichlorvos in corn oil by gavage 5 times a week for 103 weeks to groups of 50 male and 50 female Fischer rats at 0, 4, or 8 mg/kg body weight, to groups of 50 male B6C3F1 mice at 0,10, or 20 mg/Ag, and to groups of 50 female B6C3F1 mice at 0, 20, or 40 mg/kg. During the course of the studies, body weights and survival rates of the male and female rats and mice were not different from those of their respective controls; females of both species appeared to gain more weight than controls. Neoplasms induced by dichlorvos included adenomas of the exocrine pancreas (male rats), mononuclear cell leukemia (male rats), and squamous cell papilloma of the forestomach (male and female mice; two other female mice had squamous cell carcinomas). Lesions observed in female rats that may have been due to dichlorvos administration included adenomas of the exocrine pancreas and fibroadenomas of the mammary gland. The results demonstrated that dichlorvos is carcinogenic for Fischer rats and B6C3F1 mice.     

Carcinogenesis studies of dichlorvos in Fischer rats and B6C3F1 mice

Dichlorvos (dichlorovinyl dimethyl phosphoric acid ester) is a cholinesterase inhibitor used widely as a contact and stomach insecticide for control of internal and external parasites. Carcinogenesis studies were conducted by administering dichlorvos in corn oil by gavage 5 times a week for 103 weeks to groups of 50 male and 50 female Fischer rats at 0, 4, or 8 mg/kg body weight, to groups of 50 male B6C3F1 mice at 0, 10, or 20 mg/kg, and to groups of 50 female B6C3F1 mice at 0, 20, or 40 mg/kg. During the course of the studies, body weights and survival rates of the male and female rats and mice were not different from those of their respective controls; females of both species appeared to gain more weight than controls. Neoplasms induced by dichlorvos included adenomas of the exocrine pancreas (male rats), mononuclear cell leukemia (male rats), and squamous cell papilloma of the forestomach (male and female mice; two other female mice had squamous cell carcinomas). Lesions observed in female rats that may have been due to dichlorvos administration included adenomas of the exocrine pancreas and fibroadenomas of the mammary gland. The results demonstrated that dichlorvos is carcinogenic for Fischer rats and B6C3F1 mice.     

Carcinogenic effects induced in Wistar rats by combined treatment with technical-grade dichlorodiphenyltrichloroethane and sodium phenobarbital

A group of 38 female and 39 male outbred Wistar rats were treated with 500 ppm technical-grade dichlorodiphenyltrichloroethane (DDT) in the diet and 500 ppm sodium phenobarbital (PB) dissolved in drinking-water for lifespan. Twenty-three of 29 (79.3%) female and 13/28 (46.4%) male surviving animals developed primary tumours which were detected starting at 65 weeks of age. Most of the liver tumours were neoplastic nodules, but well-differentiated hepatocellular carcinomas were also found in 3 males and 5 females of the exposed animals. No liver-cell tumour was observed in 59 rats exposed to a diet containing 3% olive oil.     

NTP toxicity studies of toxicity studies of 2,4-decadienal (CAS No. 25152-84-5) administered by gavage to F344/N Rats and B6C3F1 mice

2,4-Decadienal is used as a synthetic flavoring and fragrance material and has been evaluated as a corrosion inhibitor for steel in oil field operations. 2,4-Decadienal was nominated by the National Cancer Institute for toxicity testing because the dienaldehydes occur naturally in a variety of foods and food components, are used as food additive/flavoring agents, and the potential for human exposure is high. In the toxicity studies, male and female F344/N rats and B6C3F1 mice received 2,4-decadienal (at least 93% pure) in corn oil by gavage for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral blood erythrocytes. In the 2-week studies, groups of five male and five female rats and mice received 2,4-decadienal in corn oil by gavage at doses of 0, 45, 133, 400, 1,200, or 3,600 mg 2,4-decadienal/kg body weight 5 days per week for 16 days. All animals in the 3,600 mg/kg groups were found dead or sacrificed moribund by day 3 (rats) or day 9 (mice). One 133 mg/kg female rat was found dead on day 8, and one male and one female mouse in the 1,200 mg/kg groups were found dead on days 12 and 16, respectively. At 1,200 mg/kg, treatment-related ulceration of the forestomach was observed in male and female rats and mice. Focal necrosis of the forestomach occurred in a 1,200 mg/kg female mouse. Mean body weights of all 1,200 mg/kg groups were less than those of the vehicle controls, and 1,200 mg/kg female mice lost weight during the study. Diarrhea, lethargy, abnormal breathing (rats), and thinness (mice) occurred in the 1,200 and 3,600 mg/kg groups. Gross lesions seen at necropsy included ulcerations of the forestomach in 1,200 mg/kg rats and 1,200 and 3,600 mg/kg mice. Adhesions involving the stomach and other abdominal organs were also seen in 1,200 and 3,600 mg/kg mice. In the 3-month studies, groups of 10 male and 10 female rats and mice received 2,4-decadienal in corn oil by gavage at doses of 0, 50, 100, 200, 400, or 800 mg 2,4-decadienal/kg 5 days per week for 14 weeks. No chemical-related deaths occurred. Mean body weights of 400 mg/kg male rats and 800 mg/kg male and female rats and male mice were significantly less than those of the vehicle controls. Dosed male and female rats were lethargic after week 7; the severity of the lethargy was dose related. There were changes in the leukon of dosed rats compared to vehicle control rats characterized by decreased leukocyte, lymphocyte, and eosinophil counts and increased neutrophil counts. Spleen weights of 800 mg/kg female rats and thymus weights of 400 and 800 mg/kg female rats were significantly less than those of the vehicle controls. Thymus, spleen, testis, cauda epididymis, and epididymis weights of 800 mg/kg male rats were less than those of the vehicle controls. The incidences of epithelial hyperplasia of the forestomach were significantly greater in 400 and 800 mg/kg male and female rats, 200, 400, and 800 mg/kg male mice, and 800 mg/kg female mice than in the vehicle controls. Incidences of epithelial degeneration of the forestomach were significantly increased in 800 mg/kg rats and the incidence of chronic active inflammation of the forestomach was significantly increased in 800 mg/kg female rats. Incidences of exudate and olfactory epithelial atrophy of the nose were significantly increased in 800 mg/kg male rats, and incidences of olfactory epithelial necrosis occurred in 200 mg/kg or greater mice. Olfactory epithelial hydropic degeneration occurred in a single female mouse from the 100 mg/kg group. 2,4-Decadienal was not mutagenic in any of several strains of S. typhimurium tested with and without liver S9 activation enzymes. Acute bone marrow micronucleus tests in laboratory rodents administered 2,4-decadienal by intraperitoneal injection yielded mixed results. In male rats, a single injection of 2,4-decadienal gave a positive response, but no confirmatory trial was conducted. In male mice, a standard three-injection bone marrow micronucleus experiment yielded negative results but a 48-hour bone marrow analysis after a single dose of 600 mg/kg revealed a small but statistically significant increase in micronucleated polychromatic erythrocytes. Analysis of peripheral blood erythrocytes in these same mice also showed a dose-related increase in micronucleated polychromatic cells, but the increase was insufficient for a positive call and the results of the acute micronucleus assays in mice were judged to be equivocal overall. No increase in the frequency of micronucleated normochromatic erythrocytes was seen in peripheral blood of male or female mice administered 2,4-decadienal by gavage for 3 months. In summary, 2,4-decadienal administration caused decreased body weights and increased incidences of forestomach lesions in the 3-month studies in rats and mice. In addition, treatment-related lesions of the olfactory epithelium were observed in male rats and male and female mice. The no-observed-adverse-effect level was determined to be 100 mg/kg in rats and mice. 2,4-Decadienal was not mutagenic in vitro or in vivo. Synonyms: 2,4-De; deca-2,4-dienal; trans,trans-2,4-decadienal; trans,trans-2,4-decadien-1-al; heptenyl acrolein; RIFM#77-102.     

The presence of alpha 2u-globulin is necessary for d-limonene promotion of male rat kidney tumors.

In a 2-year carcinogenesis bioassay, d-limonene (dL) induced kidney tumors in male F344 rats, but not in female F344 rats or either sex of mice, d-Limonene-1,2-oxide, a metabolite of dL, has been shown to bind reversibly the male rat-specific urinary protein, alpha2u-globulin (alpha 2u-G), lysosomal degradation than alpha 2u-G alone. This reduced degradation of alpha 2u-G-chemical complex leads to an accumulation of this protein in the proximal convoluted tubules of the male rat kidney and to the morphological changes characteristic for alpha 2u-globulin nephropathy. The only male rat strain known to be resistant to this renal disease is the alpha 2u-G deficient NCI-Black-Reiter (NBR) rat. The objectives of this study were to determine whether or not dL causes sustained increases in cell proliferation and has promoting activity for renal adenomas in male rats and if the male rat-specific urinary protein, alpha 2u-G, is required. In a 32-week initiation-promotion assay, male F344 and NBR rats were treated with either 0 or 500 ppm N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water for 2 weeks. Experimental groups of 31 to 38 rats then received 0 or 150 mg d-limonene/kg/day in corn oil for 30 weeks by p.o. gavage 5 days/week. Cell proliferation in the proximal tubules was assessed via 5-bromo-2'-deoxyuridine-filled osmotic mini-pumps and immunohistochemistry after 7 weeks (2 weeks EHEN + 5 weeks dL) and at the end of the study (2 weeks EHEN + 30 weeks dL). Preneoplastic and neoplastic lesions were quantified in perfusion-fixed kidneys. A 5-fold increase in the labeling index of P2-cells was found after 5 weeks and 30 weeks of promotion in all dL-treated F344 rats, whereas no difference between treatment groups was detected in NBR rats. No increase in tumors or preneoplastic lesions was detected in dL-treated NBR rats, whereas a 10-fold increase in renal adenomas and atypical hyperplasias was found in the EHEN-dL-treated F344 rats compared with F344 rats treated with EHEN-corn oil. d-Limonene treatment alone caused a significant increase in the number of atypical tubules and atypical hyperplasias in F344 rats when compared with the F344 vehicle control. On the other hand, a significantly lower incidence of liver tumors was found in EHEN-dL-treated F344 rats compared with F344 rats treated with EHEN-corn oil, suggesting a chemopreventative effect of dL on EHEN-induced liver carcinogenesis in F344 rats.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mammary-tumour incidence in Sprague-Dawley rats treated with 7,12-dimethylbenz(a)anthracene: effect of pregnancy and lack of effect of unilateral lactation.

Mammary teat removal (thelectomy) was performed unilaterally in female Sprague-Dawley rats at 35 days of age. They were given 7,12-dimethylbenz(a)anthracene (DMBA) when aged either 55 days or 79 days. One third were unmated; one third were mated one week and one third mated more than 3 weeks after DMBA administration. Animals were killed when tumour-positive or after one year, when mammary lesions had developed in 99% of rats. The mean latent period for adenocarcinomas was 18.9 +/- 2.0 weeks. Benign mammary tumours, mainly secretory adenomas, developed significantly later (39.2 +/- 1.7 weeks). The rapid unilateral involution of the thelectomized glands at parturition had no effect on the localization of either adenocarcinomas or benign mammary tumours. Pregnancy and delayed DMBA administration markedly reduced the incidence of adenocarcinomas; lactation had no significant effect. In a separate experiment, precocious puberty induced with pregnant-mare-serum gonadotrophin in 30-day-old female Sprague-Dawley rats enabled their first pregnancy and lactation to be completed by 80 days of age. Parity before carcinogen administration significantly delayed the development of adenocarcinomas.     

邻苯二甲酸二丁酯宫内暴露对SD大鼠两代繁殖的影响

背景与目的： 探讨邻苯二甲酸二丁酯(di-n-butyl phthalate, DBP)宫内暴露对亲代和F1代孕鼠繁殖能力以及F1和F2代雄性仔鼠生长发育及生殖系统的影响。 材料与方法： 选择妊娠SD大鼠60只,随机分为溶剂对照组(玉米油)、DBP 50 mg/(kg•d)染毒组和DBP 250 mg/(kg•d)染毒组,于GD8至GD21每日经口灌胃染毒,连续繁殖两代,观察F0及F1代孕鼠体重、产仔数、产仔性别比等的改变,以及F1和F2代雄性仔鼠体重、肛殖距、精子数目及形态、睾丸及附睾组织病理学改变。 结果： 与对照组相比,DBP 50 mg/(kg•d)组F1代母鼠哺乳期体重的增重增加(P<0.05);F2代雌性仔鼠肛殖距缩短(P<0.05),但经自身体重校正后差异无统计意义(P>0.05)。DBP 250 mg/(kg•d)组F0代母鼠哺乳期体重增重减少(P<0.05);F1代雄性仔鼠肛殖距缩短,用自身体重校正后差异显著(P<0.05);F1代雄鼠精子数目明显减少(P<0.01);F1和F2代雄性仔鼠精子头部畸形率增加(P<0.05)。 结论： 亲代宫内暴露DBP可影响F0乃至F1代孕鼠的繁殖功能,引起F1代雄性仔鼠生殖系统损伤,可能会延续至F2代。     

邻苯二甲酸二丁酯亚慢性染毒对大鼠睾丸Insl3 mRNA表达的影响

背景与目的:观察邻苯二甲酸二丁酯(DBP)亚慢性染毒对青春期大鼠睾丸间质细胞功能标志物胰岛素样因子3(Insl3)mRNA表达水平的影响。材料与方法:青春期健康雄性SD大鼠72只,随机分为3组:溶剂对照组(玉米油),DBP 50 mg/kg和250 mg/kg剂量的染毒组,每组24只。隔日染毒,等体积灌胃,连续染毒90 d。分别于染毒后30、60和90 d各组随机选取8只大鼠处死。取睾丸、附睾、心、肝、脾、肾称重并计算脏器系数,放免法检测血清睾酮含量,实时荧光定量PCR法检测睾丸Insl3 mRNA表达。结果:DBP 250 mg/kg组染毒90 d肝脏系数显著大于对照组(P<0.05);50 mg/kg组染毒60 d大鼠血清睾酮水平较对照组显著升高(P<0.05),而250 mg/kg组比50 mg/kg组显著下降(P<0.01);各染毒组大鼠睾丸Insl3 mRNA表达水平较对照组显著下调(P<0.01),染毒30 d、60 d时DBP 250 mg/kg剂量组较DBP 50 mg/kg组显著下调(P<0.05),各染毒组睾丸Insl3 mRNA表达水平均随处理时间延长先下调而后上调,60 d较30 d显著降低(P<0.05),90 d较60 d显著升高(P<0.01)。结论:青春期大鼠DBP亚慢性暴露可干扰血清睾酮及睾丸Insl3 mRNA表达水平,对肝脏可能有潜在毒性。