硝基苯对雄性小鼠生殖毒理的研究
|
摘要
硝基苯(Nitrobenzene,NB)是应用广泛的化工基础原料,也是一种毒性较强的物质,主要用于染料、医药、农药及炸药等行业,美国环保局己将其列入优先控制的污染物名单中。已有研究表明,硝基苯对哺乳动物造血、肝、肾及中枢神经系统可造成损伤,而对其生殖功能损伤的报道较少。本试验以雄性昆明小鼠为研究对象,灌胃染毒,设置三个剂量组:低剂量(26 mg/kg体重)、中剂量(52 mg/kg体重)、高剂量(105 mg/kg体重),每个剂量组设相应的空白对照和溶剂对照。其中低剂量、高剂量染毒时间为30 d,中剂量染毒时间为10 d、20 d、30 d。通过硝基苯染毒对睾丸和副性腺的毒性、对睾酮(T)、促卵泡激素(FSH)及生化指标、抗氧化功能、细胞凋亡、生殖细胞DNA损伤、Bcl-2、Bax mRNA的表达、雄激素受体(AR)表达的检测,探讨了硝基苯对雄性小鼠生殖毒性的机理。研究结果表明:
1.通过血清生化指标的检测,表明硝基苯可以导致血清中碱性磷酸酶(ALP)、琥珀酸脱氢酶(SDH)、r-谷胺酰转移酶(r-GT)、乳酸脱氢酶(LDH)活性降低,引起相应生理功能的变化并导致生精功能的障碍。
2.应用放免法和免疫组织化学法分别检测血清内T、FSH的含量和AR表达水平,证实硝基苯可以导致血清中T含量降低,FSH含量升高,说明间质细胞和支持细胞受损;而AR表达降低,削弱了AR对T转录的调节作用。影响T和FSH对生殖系统的调节功能,导致生殖系统内分泌紊乱。
3.试验结果证实硝基苯能导致睾丸和血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性下降,总抗氧化能力(T-AOC)下降,丙二醛(MDA)含量升高,表明硝基苯可引起睾丸抗氧化功能下降,诱发氧化应激,揭示氧化损伤是硝基苯致小鼠雄性生殖毒性的机制之一。
4.通过病理组织学观察、DNA Ladder、单细胞凝胶电泳(SCGE)和原位末端标记(TUNEL)法检测,说明硝基苯能够导致生殖细胞凋亡,进而引起小鼠生殖系统发生损伤。
5.应用RT-PCR法检测生殖细胞Bcl-2、Bax mRNA表达水平,表明硝基苯干扰Bcl-2、Bax mRNA的表达,Bcl-2/Bax的比值明显降低,是硝基苯导致生精细胞凋亡的机制之一。
综上所述,硝基苯可以抑制小鼠生殖功能,破坏抗氧化系统,诱导氧化应激,干扰Bcl-2、Bax mRNA,促使生殖细胞凋亡增加,进而发挥硝基苯生殖毒性作用。
本实验从器官、细胞、亚细胞和分子水平较系统地研究了硝基苯对雄性小鼠生殖系统的毒性作用,进一步探讨了硝基苯致雄性生殖机能障碍的毒理机制,丰富了毒理学知识,并为评价硝基苯的雄性生殖毒性提供科学依据。
Nitrobenzene(NB) is used extensively in dye, medicine, pesticide, dynamite and so on as basic raw material in chemical engineering. It is also a material with a high toxicity. United States Environmental Protection Agency has put it in pollutant list of priority controlling. Some studies indicated that main harm of NB was liver, kidney and central nervous system. The report is still few about the effect of NB on reproductive system of the male mice. In this test, male KM mice were divided into three dose groups(low dose(26 mg/kg), middle dose(52 mg/kg),and high dose(105 mg/kg)) and each dose group respectively included natural control group and solvent control group. Low dose group and high dose group used intragastric administration lasting 30 days, and middle dose respectively lasting 10days, 20days and 30days. After those days, those mice were killed to detected toxicity of NB to testicle and glandula accessoria, T and FSH content and biochemical indicator change, antioxidative function, apoptosis, germ cell DNA damage, the expression of Bcl-2、Bax mRNA in germ cell and AR expression in order to explore the reproductive toxicity mechanism induced by NB. The result showed as follows:
1. Detection of biochemical indicator in serum showed that NB induced decrease of ALP, SDH, r-GT and LDH activity and resulted in dysspermatogenesis.
2. The content of T, FSH and the expression level of AR were respectively detected by radioimmunity assay and immunohistochemical method. The result showed that NB leaded to the decrease of T content and the increase of FSH content, which revealed damage of interstitial cell and Sertoli's cell. NB induced the decrease of AR expression level, which weakened regulation of AR to T transcription. These findings suggested that NB affected regulation of reproductive system and resulted in endocrine disturbance of reproductive system.
3. The detection of antioxidative function revealed that the activity of SOD, CAT, GSH-Px and T-AOC were decreased and the content of MDA was increased in testis and serum. This showed that NB induced oxidative stress by the decrease of antioxidative function and this might be one of the maleness reproductive toxicity mechanism induced by NB.
4. Apoptosis was detected by pathohistology observation, DNA Ladder, SCGE and TUNEL. The result showed that NB induced germ cell apoptosis and resulted in damage of genital system in male mice.
5. The expression level of Bcl-2 and Bax mRNA was detected by RT-PCR. Bcl-2/Bax ratio was decreased obviously and this might be an important mechanism of NB inducing apoptosis.
Above all, NB inhibited reproductive function of the male mice, destroyed antioxidative function, induced oxidative stress. In addition, NB interfered with Bcl-2、Bax mRNA expression level, and induced germ cell apoptosis. All these results showed reproductive toxicity of NB.
In this study, reproductive toxicity of the male mice induced by NB was revealed from organic, cellular, subcellular and molecular level, and its toxicology mechanism was explained. These supplemented toxicology knowledge and provided evidence for evaluating male reproductive toxicity induced by NB.
1.通过血清生化指标的检测,表明硝基苯可以导致血清中碱性磷酸酶(ALP)、琥珀酸脱氢酶(SDH)、r-谷胺酰转移酶(r-GT)、乳酸脱氢酶(LDH)活性降低,引起相应生理功能的变化并导致生精功能的障碍。
2.应用放免法和免疫组织化学法分别检测血清内T、FSH的含量和AR表达水平,证实硝基苯可以导致血清中T含量降低,FSH含量升高,说明间质细胞和支持细胞受损;而AR表达降低,削弱了AR对T转录的调节作用。影响T和FSH对生殖系统的调节功能,导致生殖系统内分泌紊乱。
3.试验结果证实硝基苯能导致睾丸和血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性下降,总抗氧化能力(T-AOC)下降,丙二醛(MDA)含量升高,表明硝基苯可引起睾丸抗氧化功能下降,诱发氧化应激,揭示氧化损伤是硝基苯致小鼠雄性生殖毒性的机制之一。
4.通过病理组织学观察、DNA Ladder、单细胞凝胶电泳(SCGE)和原位末端标记(TUNEL)法检测,说明硝基苯能够导致生殖细胞凋亡,进而引起小鼠生殖系统发生损伤。
5.应用RT-PCR法检测生殖细胞Bcl-2、Bax mRNA表达水平,表明硝基苯干扰Bcl-2、Bax mRNA的表达,Bcl-2/Bax的比值明显降低,是硝基苯导致生精细胞凋亡的机制之一。
综上所述,硝基苯可以抑制小鼠生殖功能,破坏抗氧化系统,诱导氧化应激,干扰Bcl-2、Bax mRNA,促使生殖细胞凋亡增加,进而发挥硝基苯生殖毒性作用。
本实验从器官、细胞、亚细胞和分子水平较系统地研究了硝基苯对雄性小鼠生殖系统的毒性作用,进一步探讨了硝基苯致雄性生殖机能障碍的毒理机制,丰富了毒理学知识,并为评价硝基苯的雄性生殖毒性提供科学依据。
Nitrobenzene(NB) is used extensively in dye, medicine, pesticide, dynamite and so on as basic raw material in chemical engineering. It is also a material with a high toxicity. United States Environmental Protection Agency has put it in pollutant list of priority controlling. Some studies indicated that main harm of NB was liver, kidney and central nervous system. The report is still few about the effect of NB on reproductive system of the male mice. In this test, male KM mice were divided into three dose groups(low dose(26 mg/kg), middle dose(52 mg/kg),and high dose(105 mg/kg)) and each dose group respectively included natural control group and solvent control group. Low dose group and high dose group used intragastric administration lasting 30 days, and middle dose respectively lasting 10days, 20days and 30days. After those days, those mice were killed to detected toxicity of NB to testicle and glandula accessoria, T and FSH content and biochemical indicator change, antioxidative function, apoptosis, germ cell DNA damage, the expression of Bcl-2、Bax mRNA in germ cell and AR expression in order to explore the reproductive toxicity mechanism induced by NB. The result showed as follows:
1. Detection of biochemical indicator in serum showed that NB induced decrease of ALP, SDH, r-GT and LDH activity and resulted in dysspermatogenesis.
2. The content of T, FSH and the expression level of AR were respectively detected by radioimmunity assay and immunohistochemical method. The result showed that NB leaded to the decrease of T content and the increase of FSH content, which revealed damage of interstitial cell and Sertoli's cell. NB induced the decrease of AR expression level, which weakened regulation of AR to T transcription. These findings suggested that NB affected regulation of reproductive system and resulted in endocrine disturbance of reproductive system.
3. The detection of antioxidative function revealed that the activity of SOD, CAT, GSH-Px and T-AOC were decreased and the content of MDA was increased in testis and serum. This showed that NB induced oxidative stress by the decrease of antioxidative function and this might be one of the maleness reproductive toxicity mechanism induced by NB.
4. Apoptosis was detected by pathohistology observation, DNA Ladder, SCGE and TUNEL. The result showed that NB induced germ cell apoptosis and resulted in damage of genital system in male mice.
5. The expression level of Bcl-2 and Bax mRNA was detected by RT-PCR. Bcl-2/Bax ratio was decreased obviously and this might be an important mechanism of NB inducing apoptosis.
Above all, NB inhibited reproductive function of the male mice, destroyed antioxidative function, induced oxidative stress. In addition, NB interfered with Bcl-2、Bax mRNA expression level, and induced germ cell apoptosis. All these results showed reproductive toxicity of NB.
In this study, reproductive toxicity of the male mice induced by NB was revealed from organic, cellular, subcellular and molecular level, and its toxicology mechanism was explained. These supplemented toxicology knowledge and provided evidence for evaluating male reproductive toxicity induced by NB.
引文
卞建春.2003.镉的雄性动物生殖毒理学的研究.东北农业大学博士学位论文[D],12 :52-130
陈琛,李灵宏,姚武,等.1994.汞对男工生殖功能影响的研究[J].工业卫生与职业病, 20(4):221-224
程倩.1999.硝基芳烃对隆线蚤的毒性作用及QSAR研究[J].辽宁师范大学学报(自然科学版),22(2):148-152
迟宁,张衍春.1998.检出危害生物生殖的双酚A[J].日本医学介绍,19:287-289
崔涌玮,邱曙东,程健,等.2001.雄激素受体在大鼠睾丸发育过程中的表达及雄激素对其表达的调节作用[J].西安医科大学学报,22(3):193-196
崔毓桂,陈子庆,沙家豪.2004.激素对精子发生的调控[J].中华男科学,10(6):465-467
段丽菊.2005.甲醛致雄性小鼠的氧化损伤和雄性生殖遗传毒的研究[D],华中师范大学硕士学位论文,36
范奇元,顾祖维,丁训诚,等.1999.我国生殖毒理学研究进展[J].卫生毒理学杂志,13(4):247-251
费前进.2001.氧化酶对生殖细胞的影响.国外医学泌尿系统分册[J],21(增刊):170-172
顾祖维,黄文溶,钟宝珍,等.1993.应用32P后标记法检测苯灌胃后妊娠大鼠及其胎鼠体内的DNA加合物[J].卫生毒理学杂志,(增刊):191-193
韩春华,王起恩,吴萍,等.2001,硝基苯对肝癌细胞系的细胞毒性机制[J].中华预防医学杂志,35(1):48-50
贺新红,张德兴,吴燕明,等.2004.心理应激对大鼠睾丸细胞雄性激素受体表达的影响[J].中国体视学与图像分析,9(4):206-208
侯中林,王红,范凌松,等.1999.邻苯二甲酸二-2-乙基已酯对雄性大鼠的生殖毒性[J].卫生毒理学杂志,13(2):102-105
胡大林,廖建坤,欧阳小明,等.2002,苯与DNA损伤及细胞凋亡[J].医学信息,15(9):565
黄明芳,高青,孟慧林,等.1996.三硝基甲苯的雄性生殖毒性研究[J].卫生研究,25(2):72-74
江泉观,纪云晶,常元勋.2004.环境化学毒物防止手册[M].北京:化学工业出版社,725
江泉观,于永强.1994.雄(男)性生殖毒理学[M].北京:北京医科大学、中国协和医科大学联合出版社,224
李景舜,赵淑华,隋春生,等.1994.硝基苯致鼠肝脂质过氧化[J].中华劳动卫生职业病杂志,12(3):27-30
李文兰,季宇彬,杨玉楠,等.2004.邻苯二甲酸丁基苄酯的生殖毒性及其作用机制[J].环境科学,25(1):1-6
刘素嬛，王忠山．2005.成年糖尿病大鼠睾丸、附睾和前列腺内雄激素受体的表达研究[J].中华男科学杂志,11(12):891-894
芦春林,Kimmel C A,Kimmel G L,等.1993.高热致畸胎发生与热休克蛋白合成[J].卫生毒理学杂志,(增刊)135-137
陆欣,吴竞梅,徐胜,等.1996.含消炎痛IUD对家兔子宫内膜影响的酶组织化学观察[J].生殖与避孕,16(3):180-182
陆一帆,佟启良.1998.组织雄激素受体的分布、调节及运动的影响[J].北京体育大学学报,21(4):44-47
马汐平,付宝荣,刘洁,等.1999.制药废水中硝基苯致突性的细菌检测试验[J].辽宁大学学报,26(2):175-178
潘洪志,张赞萍,李省三,等.2004.慢性苯中毒小鼠DNA氧化损伤的单细胞凝胶电泳检测[J].工业卫生与职业病,30(5):286-288
秦港.2006.公鸡慢性氟中毒生殖毒性研究[D].西南大学硕士学位论文,30
沈凯.1999.生殖与避孕[M].北京:化学工业出版社,(1):11-16
史善富,汤桂秋.2002.染苯大鼠脂质过氧化和抗氧化能力的观察[J].中国医学杂志,15(2):283-285
宋晓峰,张德迎,邓永继,等.2007.邻苯二甲酸二(2-乙基)己醋诱导小鼠胚胎Leydig细胞凋亡的体外实验研究[J].中华小儿外科杂志,28(2):69-72
唐国慧,宣登峰.2003.单细胞凝胶电泳法检测二硫化碳染毒小鼠精子DNA损伤[J].中国劳动卫生职业病杂志,21(6):440-443
王金涛,李金龙,徐世文.2007.氧化应激在亚慢性镉中毒引起的肝肾细胞凋亡中的作用[J].中国兽医学报,27(3):366-368
王兴庄,邢厚娟,赵兰,等.2008.硝基苯对小鼠睾丸精原细胞和精子的影响[J].毒理学杂志,22(1):25-27
王阳峰,吕玉新.2004.用水生态毒理学方法评价13种硝基苯类化合物的急性毒性[J].新乡医学院学报,21(6):456-458
吴卫平,罗卫,胡万达,等.1991.锰对女工生殖机能的影响[J].中华劳动卫生职业病杂志,9(4):206-207
肖卫,刘小宁.2006.丙烯睛对小鼠争丸组织形态学的影响[J].中华劳动卫生职业病杂志,24(3):188
刑厚娟.2007.硝基苯对昆明小鼠亚急性毒性的研究[D].东北农业大学硕士学位论文,13
邢厚娟,王敏,徐世文.2007.氧化胁迫在硝基苯致小鼠神经毒性中的作用[J].生物技术通讯,18(4):583-585
徐镜波,杨丽,赵立群,等.2005.间二硝基苯对小鼠睾丸生殖细胞DNA损伤作用的SCGE研究[J].东北师大学报自然科学版,37(3):115-118
许清泉,朱积川,王晓峰.2005.雄激素受体敲除后雄性小鼠的泌尿生殖系统表型[J].中华泌尿外科杂志,(26)2:130-131
许庭良,姜体蓉,刘鲜林,等.1998.慢性镉中毒小鼠睾丸支持细胞及血-睾屏障超微结构观察和形态计量研究[J].中国公共卫生学报,17(1):45-46
薛良义,李卢,聂松平.2006.苯酚和对苯二酚对鲫血细胞DNA损伤的研究[J].水生生物学报,30(2):241-243
薛良义,李卢,周济胜.2005.硝基苯和氯苯对鲫鱼血细胞DNA损伤的研究[J].水利渔业,25(3):8-9
杨波,李文兰.2006.邻苯二甲酸丁基苄酯对雄性大鼠生殖系统的影响[J].哈尔滨商业大学学报,22(5):11-13
杨建明,陈琼宇,蒋学之,等.1997.金属汞经人体胎盘转运和乳汁传递及对子代生长发育的影响[J].河南医学研究,6(2):157-160
杨建明,吴向东,金泰,等.1998.镉的性腺和附性腺毒性研究[J].中华劳动卫生职业病杂志,16(1):40-42
杨建一,彭芸,李莉,等.2004.用彗星实验技术分析MTX对小鼠细胞DNA的损伤作用[J].生物技术通报,6:35-37
杨文秀,李晓英,李晏真,等.1995.苯乙烯对男(雄)性生殖功能影响的研究[J].中国公共卫生学报,14(14):288-230
杨筱珍,陈耀星,王子旭,等.2004.基因对雄性生殖细胞凋亡调控的研究进展[J].中国畜牧兽医,31(1):24-26,27
印木泉,黄建.1997.携带xylE的转基因小鼠致突变检测模型的建立及用于常规测试现状[J].中国药理学与毒理学杂志,11(2):99-100
于广丽,王海磊,程彦伟,等.2003.细胞凋亡效应期的三个关键关卡[J].河南师范大学学报,31(4)83-88
张桂元.2002.精子发生的激素调节[J].生殖医学杂志,11(5):259-263
张健,李健,王晓云,等.2002.大鼠生精小管体视学及PCNA凋亡表达的发育变化研[J].解剖学报,33(6):617-622
张晶,金明华,刘晓梅,等.2006.苯并(a)芘对小鼠肝细胞凋亡的影响[J].中国公共卫生,22(10):1242-1243
张维铭主编.2003.现代分子生物学实验手册[M].科学出版社,85-86
张育,梁虹,沈维干,等.2004.三氧化二砷对大鼠睾丸细胞酶的作用[J].中国医院药学杂志,24(8):944-946
赵兰,李金龙,邢厚娟,等.2007.硝基苯致小鼠骨髓细胞的突变作用[J].中国兽医科学,37(6):539-542
赵淑华,李景舜,王春华,等.1998.硝基苯对小鼠睾丸细胞酶的作用[J].中国公共卫生学报,17(1):39-40
甄炯,曹多志,周琳,等.2005.低浓度苯对小鼠过氧化损伤及致突变作用[J].工业卫生与职业病,31(5):283-285
郑航,胡礼泉,郑新民,等.2000.Bcl-2/Bcl-2基因表达对隐睾生殖细胞凋亡的影响[J].中华男科学杂志,14(2):81-82,85
郑履康,邓丽霞,张桥,等.1998.荧光原位杂交(FISH)检测人精子染色体非整倍体率方法的研究[J].癌变畸变突变,10(5):267-272
朱玉芬.1989.苯对雄性小鼠生殖细胞损伤的研究[J].卫生毒理学杂志,3(14):258-259
Adler B, Braun R, Schoeneich J, Boehme H.1976. Repair-Defective Mutants of Proteus Mirabilis as a Prescreening System for the Detection of Potential Carcinogens[J]. Biol Zentralbl,95: 463
Afifi N A, Ramadan A, Aziz M I, et al. 1991. Influence of Dimethoate on Testicular and Epididymal Organs,Testosterone Plasma Level and their Tissue Residuesin Rats[J]. Dtsch Tierarztl Wochenschr,98(11):419-423
Andreoli C, Leopardi P, Crebelli R. 1997. Detection of DNA Damage in Human Lymphocytes by Alkaline Single Cell Gel Electrophoresis after Exposure to Benzene or Benzene Metabolites[J]. Mut Res,37(7):95-104
Angkeow P, Deshpande S S, Qi B, et al.2002. Redox factor-1:an Extra-nuclear Role in the Regulation of Endothelial Oxidative Stress and Apoptosis[J]. Cell Death Differ,9(4):717-725
Atef M, Youssef S A.1995. Influence of Phoxim on Testicular and Seminal Vesicle Organs,Testosterone and Cholinesterase Level and its Tissue Residues in Male Rats[J]. Dtsch Tierarztl Wachenschr,102(8):1-5
Bartsch H, Malaveille C, Camus A M, et al. 1980. Validation and Comparative Studies on 180 Chemicals With Styphimurium Strains and V79 Chinese Hamster Cells in the Presence of Various Metabolizing Systems[J]. Mutat Res. 76:1-50
Beauchamp R O J, Irons R D, Rickert D E, et al.1982. A critical Review of the Literature on Nitrobenzene Toxicity[J].CRC Crit Rev Toxicol. 11(8):33-84
Bio/dynamics Inc.1984.An Inhalation Teratology Study in Rabbits With Nitrobenzene. Conducted for the Nitrobenzene Association Toxicology Task Group[J]. East Millstone,NewJersey, Bio/dynamics Inc,16 August (Project No. 83-2725; unpublished)
Bond J A, Chism J P, Rickert D E, et al.1981. Induction of Hepatic and Testicular Lesions in Fischer-344 rats by Single Oral Doses of Nitrobenzene[J]. Fundam Appl Toxicol,1(5):389-394
Burkhart J, Ankley G, Bell H, et al.2000. Strategies for Assessesing the Implications of Malformed Frogs for Environmental Health[J]. Environ Health Perspect,108(1):83-90
Burns L A, Bradley S G, Fuchs B A, et al. 1994. Immunotoxicity of Nitrobenzene in Female B6C3F1 Mice[J]. Drug Chem Toxicol,17(3):271-315
Canton J H, Slooff W, Kool H J, et al. 1985 . Toxicity Biodegradability and Accumulation of a Number of Cl/N-containing Compounds for Classification and Establishing Water Quality Criteria[J]. Regul Toxicol Pharmacol,5(2):123-31
Carlsen E-Giwercman A.1993. Evidence for Decreasing Quality of Semen During Past 50 Years[J]. Br Med,305(4):609-613
Cattley R C, Everitt J I, Gross E A, et al. 1994. Carcinogenicity and Toxicity of Inhaled Nitrobenzene in B6C3F1 Mice and F344 and SD Rats[J]. Fundam Appl Toxicol,22:328-340
Dalsenter P R, Faqi A S, Webb J, et al.1996.Reproductive Toxicity and Tissue Concentrations of Lindane in Adult Male Rats[J]. Hum Exp Toxicol,15(5):406-410
Eric A J, Harm G, Vlichiel H S, et al. 1998. Comparative Ecotoxicity of NPAHs to Larvae of the Midge Chironomus Riparius[J]. Aquatic Toxicology,(41):51-62
Gazzaniga P, Gradilone A, Vercillo R, et al.1996. Bcl-2/Bcl-2 mRNA Expression Ration as Prognostic Factor in Low-Gradeurinary Bladder Cancer[J]. Int J Cancer,69(10):100
Gilbert P, Rondelet J, Poncelet F, et al. 1980. Mutagenicity of P-nitrosophenol[J]. Food Cosmet Toxicol,18:523-525
Goldstein I, Popovici C.1960.Catalase and Peroxidase Changes in Experimental Nitrobenzene Poisoning[J]. Med Lav, 51:42-48
Hardin B D, Bond G P, SikovM R, et al. 1981. Testing of Selectworkplace Chemicals for Teratogenic Potential[J]. Scand J Work Environ Health,7(4):66-75
Holder J W. 1999. Nitrobenzene Potential Human Cancer Risk Based on Animal Studies[J]. Toxicol Ind Health,15:458-463
Huang Q G, Kong L R, Liu Y B, et al. 1996. Relationship Between Molecular Structure and Chromosomal Aberrations in Vitro Human Lymphocytes Induced by Substituted Nitrobenzenes[J]. Bull Environ Contam Toxicol,57:349-353
Husmann D A, Mcphaul M J, Wilson J D.1991. Androgen Receptor Expression in the Developing rat Prostate is not Altered by Castration Flutamide or Suppression of the Adrenal axis[J]. Endocrinology,128(4):1902-1906
Kasahara E, Sato E F, Miyoshi M, et al. 2002. Role of Oxidative Stress in Germ Cell Apoptosis Induced by di(2-ethylhexyl)Phthalate[J]. Biochem J,365(3):849-856
Kawashima K, Usami M, Sakemi K, et al. 1995. Studies on the Establishment of Appropriate Spermatogenic Endpoints for Male Infertility Disturbance in Rodent Induced by Drugs and Chemicals. I. Nitrobenzene[J]. Toxicol Sci,20:15-22
Lasier P J, Winger P V, BogenriederK J. 2000. Toxicity of Manganese to Ceriodaphnia Dubia and Hyalella Azteca[J]. Arch Environ Contam Toxicol,38(3):298-304
Lerda D.1992. Study of Sperm Character:Sties in Persons Occupationally Exposed to Lead[J]. Am J Ind Med,22(4):567-568
Levin A A, Dent J G.1982. Comparison of the Metabolism of Nitrobenzene by Hepatic Microsomes and Cecal Microflora from Fischer-344 rats in Vitro and the Relative Importance of Each in Vivo[J]. Drug Metab Dispos,10(5):450-454
Linder R E, Strader L F, Slott V L, et al. 1992. Endpoints of Spermatotoxicity in the Rat After Short Duration Exposures to Fourteen Reproductive Toxicants[J]. Reprod Toxicol. 6(6):491-505
Maness S C, McDonnell D P, Gaido K W. 1998. Inbibion of Androgen Receptor-dependent Transcriptional Activity by DDT Isomers and Methoxychlor in HepG2 Human Hepatoma Cells[J].Toxicol Appl Pharmacol,151(1):135-142
Medinsky M A, Bond J A. 1998. The Importance of Anatomical Realism for Validation ofPhysiological Models of Disposition in Inhaled Toxicants[J].Toxicol Appl Pharmacol,153(1):139-40
Mirella T, Marco G, Angelo C, et al. 2002. A P53-P66 SHC Signaling Pathwaycontrols Intracellular Redox Status Levels of Oxidation-Damaged DNA and Oxidative Stress-Induced Apoptosis[J]. Oncogene,21:3872-3878
Morgan K T, Gross E A, Bond J A, et al. 1985. Morphologic and Biochemical Studies of a Nitrobenzene-induced Encephalopathy in Rats[J]. Neurotoxicology Spring,6(1):105-116
Ohkuma Y & Kawanishi S. 1999. Oxidative DNA Damage by a Metabolite of Carcinogenic and Reproductive Toxic Nitrobenzene in the Presence of NADH and Cu(II)[J]. Biochem Biophys Res Commun,257:555-560
Oliveira C A, Mahecha G A, Carnes K, et al. 2004. Differential Homonal Regulation of Estrogen Receptors ER Alpha and ER Beta and Androgen Receptor Expression in Rat Efferent Ductules[J]. Rep Roduction,128(1):73-86
Parke D V. 1956. Studies in Detoxication. 68. The Metabolism of [14C]Nitrobenzene in the Rabbit and Guinea pig[J]. Biochem J,62(2):339-346
Probst G S, McMahon R E, Hill L E, et al. 1981. Chemically in Duced Unscheduled DNA Aynthesis in Primary Rat Hepatocyte Cultures:A comparison With Bacterial Mutagenicity Oral 218 Compounds[J]. Environ Mutagen,3:11-32
Ray A K, Chatterjee S, Ghosh S, et al. 1991. Suppressive Effect of Quinalphos on the Activity of Accessory Sex Glands and Plasma Concentrations of Gonadotrophins and Testosterone in Rats[J]. Arch Environ Contam Toxicol,21(3):383-387
Reddy B G, Pohl L R, Krishna G.1976. The Requirement of the gut Flora in Nitrobenzene-induced Methemoglobinemia in Rats. Biochem Pharmacol. 25(9):1119-1122
Rickert D E, Bond J A, Long R M, et al. 1983. Metabolism and Excretion of Nitrobenzene by Rats and Mice[J]. Toxicol Appl Pharmacol,67(2):206-214
Rina Taga, King Tang, Tetsuyuki Hattori, et al. 2005. Directacting Mutagenicity of Extracts of Coal Burning-derived Particulates and Contribution of Nitropolycyclic Aromatic Hydrocarbons[J]. Mutation Research,58(1):91-95
Robinson D, Smith J N, Williams R T. 1951. Studies in Detoxication. 40. The Metabolism of Nitrobenzene in the Rabbit;o-,m-and p-nitrophenols,o-,m-and p-aminophenols and 4-nitrocatechol as Metabolites of Nitrobenzene[J]. Biochem J,50(2):228-235
Rodriguez I, Ody C, Araki K, et al. 1997. An early and Massivewave of Germinal Cell Apoptosis is Required for the Developmeet of Functional Apermatogenesis[J]. ENIBOJ,16(9): 2262-2270
Roeleveld N, Zielhuis G A, Gabreels F. 1990. Occupational Exposure and Defects of the Central Nervous System in Offspring:Review[J]. Br J Ind Med,47(9):580-588
Russell L D. 2002. Bio Logy of Rep[J]. Roduction,66(7):950-958
Schroeder R E, Terrill J B, Lyon J P, et al .1986. An Inhalation Teratology Study in theRabbit With Nitrobenzene[J]. Toxicologist,6(11):93
Shimizu M, Yano E. 1986. Mutagenicity of Mono-nitrobenzene Derivatives in the Ames Testandrec Assay[J]. Mutat Res,170:11-22
Shinoda K, Mitsumori K, Yasuhara K, et al. 1998. Involvement of Apoptosis in the Rat Germ Cell Degeneration Induced by Nitrobenzene[J]. Arch Toxicol,72(5):296-302
Srivastava S, Seth P K, Srivastava S P. 1989. Effect of Styrene Administration on Rat Testis[J]. Archives of Toxicology,63(1):43-46
Susan C N, Frederick S, Kristna A, et al. 1997. Relative Binding Affinity Serum Modified Access (RBA SMA) Assay Predicts the Relative Invivo Bioactivity of the Xenoestrogens Bisghenol A and Octylphenol[J]. Environ Health Perspect,10(5):70-76
Svensson B G, Nise G, Erfurth E M, et al. 1992. Neuroendocrine Effects in Printing Workers Exposed to Toluene[J]. Br J Ind Med,49(6):402-408
Swinfin S T, Jackman F A. 1995. Benzene and its Industrial Derivatives New York: Halstead Press 1975 Spain J C.Biodegradation of nitroaromatic compouds[J].Annu Rev Microbio1,49:523-555
Takeda H, HakamotoT, T Kokontis J. et al.1991. Auto-regulation of Androgen Receptor Expression in Rodent prostate:Immunohistochemical and in Situ Hybridization Analysis[J]. Biochem Biophy Res Commun,177(1):488-496
Tyl R W, France K A, Fisher L C, et al.1987. Development Toxicity Evaluation of Inhaled Nitrobenzene in SD Rats[J]. Fundam Appl Toxicol,8(4):482-492
Wilmer J L, Kligerman A D, Erexson G L . 1981. Sister Chromatid Exchange Induction and Cell Cycle Inhibition by Aniline and its Metabolites in Human Fibroblasts[J].Environ Mutagen,3(7):627-638
Wirth P J, Dybing E, von Bahr C, et al. 1980. Mechanism of N-hydroxyacetylaryl-amine Mutagenicity in the Salmonella Test System: Metabolic Activation of Nhydroxyphenacetin by Liver and Kidney Fractions From Rat,Mouse,Hamster,and Man[J]. Mol Pharmacol,18:117-127
Woolveridge I, de Boer Brower M, Taylor M F, et al. 1999. Apoptosis in the rat Spermatogenic Epithelium Follvwing Withdraw l:Changes in Apoptosis Related Genes[J]. Biol Rep Rod,60:461-470
Yan W, Suomine J, Samson M, et al.2000.Involvement of Bcl-2 Family in Germ Cell Apoptosis During Testicular Development in the rat and Pro-survival Effect of Atem Cell Factor on Germ Cell in Vitro[J]. Mol Cell Endocrinol,165(2):115-129
ZHOU Tong .1999 . Molecular Mechanism Related to Cadmium Induced Carcinogenesis: Apoptosis and Changes in Expression of Protooncogenes and P53 in Male Repro Ductive Tissues of Rats[J]. Sweden,Umea Universitypress
陈琛,李灵宏,姚武,等.1994.汞对男工生殖功能影响的研究[J].工业卫生与职业病, 20(4):221-224
程倩.1999.硝基芳烃对隆线蚤的毒性作用及QSAR研究[J].辽宁师范大学学报(自然科学版),22(2):148-152
迟宁,张衍春.1998.检出危害生物生殖的双酚A[J].日本医学介绍,19:287-289
崔涌玮,邱曙东,程健,等.2001.雄激素受体在大鼠睾丸发育过程中的表达及雄激素对其表达的调节作用[J].西安医科大学学报,22(3):193-196
崔毓桂,陈子庆,沙家豪.2004.激素对精子发生的调控[J].中华男科学,10(6):465-467
段丽菊.2005.甲醛致雄性小鼠的氧化损伤和雄性生殖遗传毒的研究[D],华中师范大学硕士学位论文,36
范奇元,顾祖维,丁训诚,等.1999.我国生殖毒理学研究进展[J].卫生毒理学杂志,13(4):247-251
费前进.2001.氧化酶对生殖细胞的影响.国外医学泌尿系统分册[J],21(增刊):170-172
顾祖维,黄文溶,钟宝珍,等.1993.应用32P后标记法检测苯灌胃后妊娠大鼠及其胎鼠体内的DNA加合物[J].卫生毒理学杂志,(增刊):191-193
韩春华,王起恩,吴萍,等.2001,硝基苯对肝癌细胞系的细胞毒性机制[J].中华预防医学杂志,35(1):48-50
贺新红,张德兴,吴燕明,等.2004.心理应激对大鼠睾丸细胞雄性激素受体表达的影响[J].中国体视学与图像分析,9(4):206-208
侯中林,王红,范凌松,等.1999.邻苯二甲酸二-2-乙基已酯对雄性大鼠的生殖毒性[J].卫生毒理学杂志,13(2):102-105
胡大林,廖建坤,欧阳小明,等.2002,苯与DNA损伤及细胞凋亡[J].医学信息,15(9):565
黄明芳,高青,孟慧林,等.1996.三硝基甲苯的雄性生殖毒性研究[J].卫生研究,25(2):72-74
江泉观,纪云晶,常元勋.2004.环境化学毒物防止手册[M].北京:化学工业出版社,725
江泉观,于永强.1994.雄(男)性生殖毒理学[M].北京:北京医科大学、中国协和医科大学联合出版社,224
李景舜,赵淑华,隋春生,等.1994.硝基苯致鼠肝脂质过氧化[J].中华劳动卫生职业病杂志,12(3):27-30
李文兰,季宇彬,杨玉楠,等.2004.邻苯二甲酸丁基苄酯的生殖毒性及其作用机制[J].环境科学,25(1):1-6
刘素嬛，王忠山．2005.成年糖尿病大鼠睾丸、附睾和前列腺内雄激素受体的表达研究[J].中华男科学杂志,11(12):891-894
芦春林,Kimmel C A,Kimmel G L,等.1993.高热致畸胎发生与热休克蛋白合成[J].卫生毒理学杂志,(增刊)135-137
陆欣,吴竞梅,徐胜,等.1996.含消炎痛IUD对家兔子宫内膜影响的酶组织化学观察[J].生殖与避孕,16(3):180-182
陆一帆,佟启良.1998.组织雄激素受体的分布、调节及运动的影响[J].北京体育大学学报,21(4):44-47
马汐平,付宝荣,刘洁,等.1999.制药废水中硝基苯致突性的细菌检测试验[J].辽宁大学学报,26(2):175-178
潘洪志,张赞萍,李省三,等.2004.慢性苯中毒小鼠DNA氧化损伤的单细胞凝胶电泳检测[J].工业卫生与职业病,30(5):286-288
秦港.2006.公鸡慢性氟中毒生殖毒性研究[D].西南大学硕士学位论文,30
沈凯.1999.生殖与避孕[M].北京:化学工业出版社,(1):11-16
史善富,汤桂秋.2002.染苯大鼠脂质过氧化和抗氧化能力的观察[J].中国医学杂志,15(2):283-285
宋晓峰,张德迎,邓永继,等.2007.邻苯二甲酸二(2-乙基)己醋诱导小鼠胚胎Leydig细胞凋亡的体外实验研究[J].中华小儿外科杂志,28(2):69-72
唐国慧,宣登峰.2003.单细胞凝胶电泳法检测二硫化碳染毒小鼠精子DNA损伤[J].中国劳动卫生职业病杂志,21(6):440-443
王金涛,李金龙,徐世文.2007.氧化应激在亚慢性镉中毒引起的肝肾细胞凋亡中的作用[J].中国兽医学报,27(3):366-368
王兴庄,邢厚娟,赵兰,等.2008.硝基苯对小鼠睾丸精原细胞和精子的影响[J].毒理学杂志,22(1):25-27
王阳峰,吕玉新.2004.用水生态毒理学方法评价13种硝基苯类化合物的急性毒性[J].新乡医学院学报,21(6):456-458
吴卫平,罗卫,胡万达,等.1991.锰对女工生殖机能的影响[J].中华劳动卫生职业病杂志,9(4):206-207
肖卫,刘小宁.2006.丙烯睛对小鼠争丸组织形态学的影响[J].中华劳动卫生职业病杂志,24(3):188
刑厚娟.2007.硝基苯对昆明小鼠亚急性毒性的研究[D].东北农业大学硕士学位论文,13
邢厚娟,王敏,徐世文.2007.氧化胁迫在硝基苯致小鼠神经毒性中的作用[J].生物技术通讯,18(4):583-585
徐镜波,杨丽,赵立群,等.2005.间二硝基苯对小鼠睾丸生殖细胞DNA损伤作用的SCGE研究[J].东北师大学报自然科学版,37(3):115-118
许清泉,朱积川,王晓峰.2005.雄激素受体敲除后雄性小鼠的泌尿生殖系统表型[J].中华泌尿外科杂志,(26)2:130-131
许庭良,姜体蓉,刘鲜林,等.1998.慢性镉中毒小鼠睾丸支持细胞及血-睾屏障超微结构观察和形态计量研究[J].中国公共卫生学报,17(1):45-46
薛良义,李卢,聂松平.2006.苯酚和对苯二酚对鲫血细胞DNA损伤的研究[J].水生生物学报,30(2):241-243
薛良义,李卢,周济胜.2005.硝基苯和氯苯对鲫鱼血细胞DNA损伤的研究[J].水利渔业,25(3):8-9
杨波,李文兰.2006.邻苯二甲酸丁基苄酯对雄性大鼠生殖系统的影响[J].哈尔滨商业大学学报,22(5):11-13
杨建明,陈琼宇,蒋学之,等.1997.金属汞经人体胎盘转运和乳汁传递及对子代生长发育的影响[J].河南医学研究,6(2):157-160
杨建明,吴向东,金泰,等.1998.镉的性腺和附性腺毒性研究[J].中华劳动卫生职业病杂志,16(1):40-42
杨建一,彭芸,李莉,等.2004.用彗星实验技术分析MTX对小鼠细胞DNA的损伤作用[J].生物技术通报,6:35-37
杨文秀,李晓英,李晏真,等.1995.苯乙烯对男(雄)性生殖功能影响的研究[J].中国公共卫生学报,14(14):288-230
杨筱珍,陈耀星,王子旭,等.2004.基因对雄性生殖细胞凋亡调控的研究进展[J].中国畜牧兽医,31(1):24-26,27
印木泉,黄建.1997.携带xylE的转基因小鼠致突变检测模型的建立及用于常规测试现状[J].中国药理学与毒理学杂志,11(2):99-100
于广丽,王海磊,程彦伟,等.2003.细胞凋亡效应期的三个关键关卡[J].河南师范大学学报,31(4)83-88
张桂元.2002.精子发生的激素调节[J].生殖医学杂志,11(5):259-263
张健,李健,王晓云,等.2002.大鼠生精小管体视学及PCNA凋亡表达的发育变化研[J].解剖学报,33(6):617-622
张晶,金明华,刘晓梅,等.2006.苯并(a)芘对小鼠肝细胞凋亡的影响[J].中国公共卫生,22(10):1242-1243
张维铭主编.2003.现代分子生物学实验手册[M].科学出版社,85-86
张育,梁虹,沈维干,等.2004.三氧化二砷对大鼠睾丸细胞酶的作用[J].中国医院药学杂志,24(8):944-946
赵兰,李金龙,邢厚娟,等.2007.硝基苯致小鼠骨髓细胞的突变作用[J].中国兽医科学,37(6):539-542
赵淑华,李景舜,王春华,等.1998.硝基苯对小鼠睾丸细胞酶的作用[J].中国公共卫生学报,17(1):39-40
甄炯,曹多志,周琳,等.2005.低浓度苯对小鼠过氧化损伤及致突变作用[J].工业卫生与职业病,31(5):283-285
郑航,胡礼泉,郑新民,等.2000.Bcl-2/Bcl-2基因表达对隐睾生殖细胞凋亡的影响[J].中华男科学杂志,14(2):81-82,85
郑履康,邓丽霞,张桥,等.1998.荧光原位杂交(FISH)检测人精子染色体非整倍体率方法的研究[J].癌变畸变突变,10(5):267-272
朱玉芬.1989.苯对雄性小鼠生殖细胞损伤的研究[J].卫生毒理学杂志,3(14):258-259
Adler B, Braun R, Schoeneich J, Boehme H.1976. Repair-Defective Mutants of Proteus Mirabilis as a Prescreening System for the Detection of Potential Carcinogens[J]. Biol Zentralbl,95: 463
Afifi N A, Ramadan A, Aziz M I, et al. 1991. Influence of Dimethoate on Testicular and Epididymal Organs,Testosterone Plasma Level and their Tissue Residuesin Rats[J]. Dtsch Tierarztl Wochenschr,98(11):419-423
Andreoli C, Leopardi P, Crebelli R. 1997. Detection of DNA Damage in Human Lymphocytes by Alkaline Single Cell Gel Electrophoresis after Exposure to Benzene or Benzene Metabolites[J]. Mut Res,37(7):95-104
Angkeow P, Deshpande S S, Qi B, et al.2002. Redox factor-1:an Extra-nuclear Role in the Regulation of Endothelial Oxidative Stress and Apoptosis[J]. Cell Death Differ,9(4):717-725
Atef M, Youssef S A.1995. Influence of Phoxim on Testicular and Seminal Vesicle Organs,Testosterone and Cholinesterase Level and its Tissue Residues in Male Rats[J]. Dtsch Tierarztl Wachenschr,102(8):1-5
Bartsch H, Malaveille C, Camus A M, et al. 1980. Validation and Comparative Studies on 180 Chemicals With Styphimurium Strains and V79 Chinese Hamster Cells in the Presence of Various Metabolizing Systems[J]. Mutat Res. 76:1-50
Beauchamp R O J, Irons R D, Rickert D E, et al.1982. A critical Review of the Literature on Nitrobenzene Toxicity[J].CRC Crit Rev Toxicol. 11(8):33-84
Bio/dynamics Inc.1984.An Inhalation Teratology Study in Rabbits With Nitrobenzene. Conducted for the Nitrobenzene Association Toxicology Task Group[J]. East Millstone,NewJersey, Bio/dynamics Inc,16 August (Project No. 83-2725; unpublished)
Bond J A, Chism J P, Rickert D E, et al.1981. Induction of Hepatic and Testicular Lesions in Fischer-344 rats by Single Oral Doses of Nitrobenzene[J]. Fundam Appl Toxicol,1(5):389-394
Burkhart J, Ankley G, Bell H, et al.2000. Strategies for Assessesing the Implications of Malformed Frogs for Environmental Health[J]. Environ Health Perspect,108(1):83-90
Burns L A, Bradley S G, Fuchs B A, et al. 1994. Immunotoxicity of Nitrobenzene in Female B6C3F1 Mice[J]. Drug Chem Toxicol,17(3):271-315
Canton J H, Slooff W, Kool H J, et al. 1985 . Toxicity Biodegradability and Accumulation of a Number of Cl/N-containing Compounds for Classification and Establishing Water Quality Criteria[J]. Regul Toxicol Pharmacol,5(2):123-31
Carlsen E-Giwercman A.1993. Evidence for Decreasing Quality of Semen During Past 50 Years[J]. Br Med,305(4):609-613
Cattley R C, Everitt J I, Gross E A, et al. 1994. Carcinogenicity and Toxicity of Inhaled Nitrobenzene in B6C3F1 Mice and F344 and SD Rats[J]. Fundam Appl Toxicol,22:328-340
Dalsenter P R, Faqi A S, Webb J, et al.1996.Reproductive Toxicity and Tissue Concentrations of Lindane in Adult Male Rats[J]. Hum Exp Toxicol,15(5):406-410
Eric A J, Harm G, Vlichiel H S, et al. 1998. Comparative Ecotoxicity of NPAHs to Larvae of the Midge Chironomus Riparius[J]. Aquatic Toxicology,(41):51-62
Gazzaniga P, Gradilone A, Vercillo R, et al.1996. Bcl-2/Bcl-2 mRNA Expression Ration as Prognostic Factor in Low-Gradeurinary Bladder Cancer[J]. Int J Cancer,69(10):100
Gilbert P, Rondelet J, Poncelet F, et al. 1980. Mutagenicity of P-nitrosophenol[J]. Food Cosmet Toxicol,18:523-525
Goldstein I, Popovici C.1960.Catalase and Peroxidase Changes in Experimental Nitrobenzene Poisoning[J]. Med Lav, 51:42-48
Hardin B D, Bond G P, SikovM R, et al. 1981. Testing of Selectworkplace Chemicals for Teratogenic Potential[J]. Scand J Work Environ Health,7(4):66-75
Holder J W. 1999. Nitrobenzene Potential Human Cancer Risk Based on Animal Studies[J]. Toxicol Ind Health,15:458-463
Huang Q G, Kong L R, Liu Y B, et al. 1996. Relationship Between Molecular Structure and Chromosomal Aberrations in Vitro Human Lymphocytes Induced by Substituted Nitrobenzenes[J]. Bull Environ Contam Toxicol,57:349-353
Husmann D A, Mcphaul M J, Wilson J D.1991. Androgen Receptor Expression in the Developing rat Prostate is not Altered by Castration Flutamide or Suppression of the Adrenal axis[J]. Endocrinology,128(4):1902-1906
Kasahara E, Sato E F, Miyoshi M, et al. 2002. Role of Oxidative Stress in Germ Cell Apoptosis Induced by di(2-ethylhexyl)Phthalate[J]. Biochem J,365(3):849-856
Kawashima K, Usami M, Sakemi K, et al. 1995. Studies on the Establishment of Appropriate Spermatogenic Endpoints for Male Infertility Disturbance in Rodent Induced by Drugs and Chemicals. I. Nitrobenzene[J]. Toxicol Sci,20:15-22
Lasier P J, Winger P V, BogenriederK J. 2000. Toxicity of Manganese to Ceriodaphnia Dubia and Hyalella Azteca[J]. Arch Environ Contam Toxicol,38(3):298-304
Lerda D.1992. Study of Sperm Character:Sties in Persons Occupationally Exposed to Lead[J]. Am J Ind Med,22(4):567-568
Levin A A, Dent J G.1982. Comparison of the Metabolism of Nitrobenzene by Hepatic Microsomes and Cecal Microflora from Fischer-344 rats in Vitro and the Relative Importance of Each in Vivo[J]. Drug Metab Dispos,10(5):450-454
Linder R E, Strader L F, Slott V L, et al. 1992. Endpoints of Spermatotoxicity in the Rat After Short Duration Exposures to Fourteen Reproductive Toxicants[J]. Reprod Toxicol. 6(6):491-505
Maness S C, McDonnell D P, Gaido K W. 1998. Inbibion of Androgen Receptor-dependent Transcriptional Activity by DDT Isomers and Methoxychlor in HepG2 Human Hepatoma Cells[J].Toxicol Appl Pharmacol,151(1):135-142
Medinsky M A, Bond J A. 1998. The Importance of Anatomical Realism for Validation ofPhysiological Models of Disposition in Inhaled Toxicants[J].Toxicol Appl Pharmacol,153(1):139-40
Mirella T, Marco G, Angelo C, et al. 2002. A P53-P66 SHC Signaling Pathwaycontrols Intracellular Redox Status Levels of Oxidation-Damaged DNA and Oxidative Stress-Induced Apoptosis[J]. Oncogene,21:3872-3878
Morgan K T, Gross E A, Bond J A, et al. 1985. Morphologic and Biochemical Studies of a Nitrobenzene-induced Encephalopathy in Rats[J]. Neurotoxicology Spring,6(1):105-116
Ohkuma Y & Kawanishi S. 1999. Oxidative DNA Damage by a Metabolite of Carcinogenic and Reproductive Toxic Nitrobenzene in the Presence of NADH and Cu(II)[J]. Biochem Biophys Res Commun,257:555-560
Oliveira C A, Mahecha G A, Carnes K, et al. 2004. Differential Homonal Regulation of Estrogen Receptors ER Alpha and ER Beta and Androgen Receptor Expression in Rat Efferent Ductules[J]. Rep Roduction,128(1):73-86
Parke D V. 1956. Studies in Detoxication. 68. The Metabolism of [14C]Nitrobenzene in the Rabbit and Guinea pig[J]. Biochem J,62(2):339-346
Probst G S, McMahon R E, Hill L E, et al. 1981. Chemically in Duced Unscheduled DNA Aynthesis in Primary Rat Hepatocyte Cultures:A comparison With Bacterial Mutagenicity Oral 218 Compounds[J]. Environ Mutagen,3:11-32
Ray A K, Chatterjee S, Ghosh S, et al. 1991. Suppressive Effect of Quinalphos on the Activity of Accessory Sex Glands and Plasma Concentrations of Gonadotrophins and Testosterone in Rats[J]. Arch Environ Contam Toxicol,21(3):383-387
Reddy B G, Pohl L R, Krishna G.1976. The Requirement of the gut Flora in Nitrobenzene-induced Methemoglobinemia in Rats. Biochem Pharmacol. 25(9):1119-1122
Rickert D E, Bond J A, Long R M, et al. 1983. Metabolism and Excretion of Nitrobenzene by Rats and Mice[J]. Toxicol Appl Pharmacol,67(2):206-214
Rina Taga, King Tang, Tetsuyuki Hattori, et al. 2005. Directacting Mutagenicity of Extracts of Coal Burning-derived Particulates and Contribution of Nitropolycyclic Aromatic Hydrocarbons[J]. Mutation Research,58(1):91-95
Robinson D, Smith J N, Williams R T. 1951. Studies in Detoxication. 40. The Metabolism of Nitrobenzene in the Rabbit;o-,m-and p-nitrophenols,o-,m-and p-aminophenols and 4-nitrocatechol as Metabolites of Nitrobenzene[J]. Biochem J,50(2):228-235
Rodriguez I, Ody C, Araki K, et al. 1997. An early and Massivewave of Germinal Cell Apoptosis is Required for the Developmeet of Functional Apermatogenesis[J]. ENIBOJ,16(9): 2262-2270
Roeleveld N, Zielhuis G A, Gabreels F. 1990. Occupational Exposure and Defects of the Central Nervous System in Offspring:Review[J]. Br J Ind Med,47(9):580-588
Russell L D. 2002. Bio Logy of Rep[J]. Roduction,66(7):950-958
Schroeder R E, Terrill J B, Lyon J P, et al .1986. An Inhalation Teratology Study in theRabbit With Nitrobenzene[J]. Toxicologist,6(11):93
Shimizu M, Yano E. 1986. Mutagenicity of Mono-nitrobenzene Derivatives in the Ames Testandrec Assay[J]. Mutat Res,170:11-22
Shinoda K, Mitsumori K, Yasuhara K, et al. 1998. Involvement of Apoptosis in the Rat Germ Cell Degeneration Induced by Nitrobenzene[J]. Arch Toxicol,72(5):296-302
Srivastava S, Seth P K, Srivastava S P. 1989. Effect of Styrene Administration on Rat Testis[J]. Archives of Toxicology,63(1):43-46
Susan C N, Frederick S, Kristna A, et al. 1997. Relative Binding Affinity Serum Modified Access (RBA SMA) Assay Predicts the Relative Invivo Bioactivity of the Xenoestrogens Bisghenol A and Octylphenol[J]. Environ Health Perspect,10(5):70-76
Svensson B G, Nise G, Erfurth E M, et al. 1992. Neuroendocrine Effects in Printing Workers Exposed to Toluene[J]. Br J Ind Med,49(6):402-408
Swinfin S T, Jackman F A. 1995. Benzene and its Industrial Derivatives New York: Halstead Press 1975 Spain J C.Biodegradation of nitroaromatic compouds[J].Annu Rev Microbio1,49:523-555
Takeda H, HakamotoT, T Kokontis J. et al.1991. Auto-regulation of Androgen Receptor Expression in Rodent prostate:Immunohistochemical and in Situ Hybridization Analysis[J]. Biochem Biophy Res Commun,177(1):488-496
Tyl R W, France K A, Fisher L C, et al.1987. Development Toxicity Evaluation of Inhaled Nitrobenzene in SD Rats[J]. Fundam Appl Toxicol,8(4):482-492
Wilmer J L, Kligerman A D, Erexson G L . 1981. Sister Chromatid Exchange Induction and Cell Cycle Inhibition by Aniline and its Metabolites in Human Fibroblasts[J].Environ Mutagen,3(7):627-638
Wirth P J, Dybing E, von Bahr C, et al. 1980. Mechanism of N-hydroxyacetylaryl-amine Mutagenicity in the Salmonella Test System: Metabolic Activation of Nhydroxyphenacetin by Liver and Kidney Fractions From Rat,Mouse,Hamster,and Man[J]. Mol Pharmacol,18:117-127
Woolveridge I, de Boer Brower M, Taylor M F, et al. 1999. Apoptosis in the rat Spermatogenic Epithelium Follvwing Withdraw l:Changes in Apoptosis Related Genes[J]. Biol Rep Rod,60:461-470
Yan W, Suomine J, Samson M, et al.2000.Involvement of Bcl-2 Family in Germ Cell Apoptosis During Testicular Development in the rat and Pro-survival Effect of Atem Cell Factor on Germ Cell in Vitro[J]. Mol Cell Endocrinol,165(2):115-129
ZHOU Tong .1999 . Molecular Mechanism Related to Cadmium Induced Carcinogenesis: Apoptosis and Changes in Expression of Protooncogenes and P53 in Male Repro Ductive Tissues of Rats[J]. Sweden,Umea Universitypress