国家毒理学计划对雌性斯普拉格-道利大鼠进行磁场促进(二甲基苯并蒽引发)的研究(全身暴露/灌胃研究)。
NTP Studies of Magnetic Field Promotion (DMBA Initiation) in Female Sprague-Dawley Rats (Whole-body Exposure/Gavage Studies).
出版信息
Natl Toxicol Program Tech Rep Ser. 1999 Aug;489:1-148.
Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus, the potential for human exposure is high. These elec-tric and magnetic fields are predominantly of low fre-quency (60 Hz in the United States and 50 Hz in Europe) and generally of low intensity. Because some epidemiology studies and initiation/promotion studies in rats have suggested a potential for increased breast cancer rates with increasing magnetic field exposure, the ability of 50- and 60-Hz magnetic fields to pro-mote mammary gland tumors initiated by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) was examined in female Sprague-Dawley rats in 13- and 26-week whole-body exposure studies. Additional animals were evaluated for changes in pineal gland and serum melatonin concentrations. FIRST 13-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were ad-ministered 20 mg DMBA (four weekly gavage doses of 5 mg in sesame oil) and exposed to 1 G 50-Hz, 5 G 50-Hz, or 1 G 60-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 13 weeks. A group of 100 rats administered 20 mg DMBA served as DMBA controls. A group of 100 vehicle control rats was administered only sesame oil on the same schedule. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. All vehicle control rats survived to the end of the study. Of the animals administered 20 mg DMBA, 6 rats in the DMBA control group, 13 in the DMBA/1 G 50-Hz group, eight in the DMBA/5 G 50-Hz group, and five in the DMBA/1 G 60-Hz group died or were removed from the study prior to the final necropsy. Final mean body weights and body weight gains of the DMBA/1 G 50-Hz and DMBA/1 G 60-Hz groups and the mean body weight gain of the DMBA/5 G 50-Hz group were slightly greater than those of the DMBA control group. Clinical findings including torso masses and ulcers (on the mammary masses) were attributed to DMBA administration. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA control group. Relative to the DMBA control group, exposure to magnetic fields did not significantly affect overall incidences of mammary gland neoplasms or nonneoplastic lesions in the DMBA/magnetic field groups. SECOND 13-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were ad-ministered 8 mg DMBA (four weekly gavage doses of 2 mg in sesame oil) and exposed to 1 G 50-Hz or 5 G 50-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 13 weeks. A group of 100 female rats administered 8 mg DMBA served as DMBA controls. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. Except for one rat in the DMBA/5 G 50-Hz group, all rats survived until the end of the study. Final mean body weights of DMBA/magnetic field groups were similar to those of the DMBA control group. Clinical findings including torso masses and ulcers were attributed to DMBA administration. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA control group. Relative to the DMBA control group, exposure to magnetic fields did not significantly affect overall incidences of mammary gland neoplasms or nonneoplastic lesions in the DMBA/magnetic field groups. 26-WEEK STUDY: Groups of 100 female Sprague-Dawley rats were administered 10 mg DMBA (in sesame oil) by gavage followed by exposure to 1 G 50-Hz, 5 G 50-Hz, or 1 G 60-Hz magnetic fields for 18.5 hours per day, 7 days per week, for 26 weeks. A group of 100 female rats administered 10 mg DMBA served as DMBA controls. Another 100 vehicle control rats were administered only sesame oil. Additional groups of 10 rats receiving similar treatment were evaluated for pineal gland and serum melatonin concentrations at 4, 8, or 12 weeks. All rats in the vehicle control group survived until the end of the study. Twelve rats in the DMBA control group, 15 in the DMBA/1 G 50-Hz group, 9 in the DMBA/5 G 50-Hz group, and six in the DMBA/1 G 60-Hz group died or were removed during the study. The final mean body weights and body weight gains of the DMBA/1 G 50-Hz and DMBA/5 G 50-Hz groups were significantly greater than those of the DMBA control group. Clinical findings including torso masses, abscesses, and ulcers were attributed to DMBA administration. The pineal gland melatonin concentrations of DMBA/5 G 50-Hz and DMBA/1 G 60-Hz rats were significantly greater than that of the DMBA controls at week 12; however, these data were highly variable between individual animals within each group. The numbers of palpable mammary gland tumors, tumor sizes, and total tumor areas in DMBA/magnetic field groups were similar to those in the DMBA controls. The incidences of mammary gland carci-noma (including multiple) in the DMBA/1 G 60-Hz group were significantly decreased relative to the DMBA control group. CONCLUSIONS: In an initiation/promotion study in which female Sprague-Dawley rats were initiated by four weekly doses of 5 mg DMBA per rat beginning at 50 days of age and exposed to 50-Hz magnetic fields at 1 or 5 G field intensities or to 1 G 60-Hz magnetic fields for 13 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms. The prevalence and multiplicity of mammary gland carcinomas in all DMBA groups limited the ability of this assay to detect a promoting effect of magnetic fields. In an initiation/promotion study in which female Sprague-Dawley rats were initiated by four weekly doses of 2 mg DMBA per rat beginning at 50 days of age and exposed to 50-Hz magnetic fields at 1 or 5 G field intensities for 13 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms. In an initiation/promotion study in which female Sprague-Dawley rats were initiated by a single 10 mg DMBA dose at 50 days of age and then exposed to 50-Hz magnetic fields at 1 or 5 G field intensities or to 1 G 60-Hz magnetic fields for 26 weeks, there was no evidence that magnetic fields promoted the development of mammary gland neoplasms.
电场和磁场与电的生产、传输及使用相关联;因此,人类暴露于其中的可能性很高。这些电场和磁场主要是低频的(在美国为60赫兹,在欧洲为50赫兹),且强度一般较低。由于一些流行病学研究以及对大鼠的启动/促进研究表明,随着磁场暴露增加,患乳腺癌的几率可能会上升,因此在13周和26周的全身暴露研究中,对雌性斯普拉格-道利大鼠进行了检测,以研究50赫兹和60赫兹磁场对由7,12-二甲基苯并(a)蒽(DMBA)诱发的乳腺肿瘤的促进作用。另外,还对动物的松果体和血清褪黑素浓度变化进行了评估。
第一项13周研究:将100只雌性斯普拉格-道利大鼠分为几组,每只大鼠每周经口灌胃给予4次、每次5毫克溶解于芝麻油中的20毫克DMBA,并每天暴露于1高斯50赫兹、5高斯50赫兹或1高斯60赫兹的磁场中,每周7天,共13周。一组给予20毫克DMBA的100只大鼠作为DMBA对照组。一组100只溶剂对照组大鼠按相同时间表仅给予芝麻油。另外几组接受类似处理的10只大鼠在第4、8或12周时评估其松果体和血清褪黑素浓度。所有溶剂对照组大鼠均存活至研究结束。在给予20毫克DMBA的动物中(DMBA对照组),有6只大鼠、DMBA/1高斯50赫兹组有13只大鼠、DMBA/5高斯50赫兹组有8只大鼠以及DMBA/1高斯60赫兹组有5只大鼠在最终尸检前死亡或被移出研究。DMBA/1高斯50赫兹组和DMBA/1高斯60赫兹组的最终平均体重和体重增加量以及DMBA/5高斯50赫兹组的平均体重增加量略高于DMBA对照组。包括躯干肿块和溃疡(乳腺肿块上的)在内的临床发现归因于DMBA给药。DMBA/磁场组中可触及的乳腺肿瘤数量、肿瘤大小和总肿瘤面积与DMBA对照组相似。相对于DMBA对照组,暴露于磁场并未显著影响DMBA/磁场组中乳腺肿瘤或非肿瘤性病变的总体发生率。
第二项13周研究:将100只雌性斯普拉格-道利大鼠分为几组,每只大鼠每周经口灌胃给予4次、每次2毫克溶解于芝麻油中的8毫克DMBA,并每天暴露于1高斯50赫兹或5高斯50赫兹的磁场中,每周7天,共13周。一组给予8毫克DMBA的100只雌性大鼠作为DMBA对照组。另外几组接受类似处理的10只大鼠在第4、8或12周时评估其松果体和血清褪黑素浓度。除了DMBA/5高斯50赫兹组的一只大鼠外,所有大鼠均存活至研究结束。DMBA/磁场组的最终平均体重与DMBA对照组相似。包括躯干肿块和溃疡在内的临床发现归因于DMBA给药。DMBA/磁场组中可触及的乳腺肿瘤数量、肿瘤大小和总肿瘤面积与DMBA对照组相似。相对于DMBA对照组,暴露于磁场并未显著影响DMBA/磁场组中乳腺肿瘤或非肿瘤性病变的总体发生率。
26周研究:将100只雌性斯普拉格-道利大鼠分为几组,每只大鼠经口灌胃给予10毫克(溶于芝麻油中)DMBA,随后每天暴露于1高斯50赫兹、5高斯50赫兹或1高斯60赫兹的磁场中,每周7天,共26周。一组给予10毫克DMBA的100只雌性大鼠作为DMBA对照组。另外100只溶剂对照组大鼠仅给予芝麻油。另外几组接受类似处理的10只大鼠在第4、8或12周时评估其松果体和血清褪黑素浓度。溶剂对照组的所有大鼠均存活至研究结束。DMBA对照组中有12只大鼠、DMBA/1高斯50赫兹组中有15只大鼠、DMBA/5高斯50赫兹组中有9只大鼠以及DMBA/1高斯60赫兹组中有6只大鼠在研究期间死亡或被移出。DMBA/1高斯50赫兹组和DMBA/5高斯50赫兹组的最终平均体重和体重增加量显著高于DMBA对照组。包括躯干肿块、脓肿和溃疡在内的临床发现归因于DMBA给药。在第12周时,DMBA/5高斯50赫兹组和DMBA/1高斯60赫兹组大鼠的松果体褪黑素浓度显著高于DMBA对照组;然而,这些数据在每组内的个体动物之间差异很大。DMBA/磁场组中可触及的乳腺肿瘤数量、肿瘤大小和总肿瘤面积与DMBA对照组相似。相对于DMBA对照组,DMBA/1高斯60赫兹组中乳腺癌(包括多发性)的发生率显著降低。
结论
在一项启动/促进研究中,雌性斯普拉格-道利大鼠从50日龄开始每周4次、每次每只大鼠给予5毫克DMBA进行启动,并暴露于1高斯或5高斯场强的50赫兹磁场或1高斯60赫兹磁场中13周,没有证据表明磁场促进了乳腺肿瘤的发展。所有DMBA组中乳腺癌的患病率和多发性限制了该试验检测磁场促进作用的能力。在一项启动/促进研究中,雌性斯普拉格-道利大鼠从50日龄开始每周4次、每次每只大鼠给予2毫克DMBA进行启动,并暴露于1高斯或5高斯场强的50赫兹磁场中13周,没有证据表明磁场促进了乳腺肿瘤的发展。在一项启动/促进研究中,雌性斯普拉格-道利大鼠在50日龄时单次给予10毫克DMBA启动,然后暴露于1高斯或5高斯场强的50赫兹磁场或1高斯60赫兹磁场中26周,没有证据表明磁场促进了乳腺肿瘤的发展。