A LIFETIME ONCOGENICITY STUDY IN RATS WITH ACRYLAMIDE
A LIFETIME ONCOGENICITY STUDY IN RATS WITH ACRYLAMIDE
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DOI：
10.1006/faat.1995.1112
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发表时间：
1995-08-01
期刊：
影响因子：
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通讯作者：
STEDHAM, MA
中科院分区：
文献类型：
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作者：
FRIEDMAN, MA;DULAK, LH;STEDHAM, MA
在Fischer 344大鼠中进行了终生致癌性研究，以准确表征丙烯酰胺的致癌效力。在为期106周的研究中，丙烯酰胺被添加到饮用水中，其浓度为男性每天0、0.1、0.5或2.0 mg/kg，女性每天0、1.0或3.0 mg/kg。所有实验动物均进行了完整的尸检和大体病理检查。对所有高剂量动物和对照动物的组织进行组织病理学检查。从中剂量组和低剂量组中选择的组织进行组织病理学检查，以澄清高剂量组和对照组的观察结果。在任何研究动物中没有观察到神经毒性，但在雄性和雌性高剂量组中观察到坐骨神经变性。从第17个月到研究结束，高剂量男性组和高剂量女性组在第24个月观察到与丙烯酰胺相关的死亡率增加。高剂量男性组睾丸束膜间皮瘤明显增加。两组女性服用丙烯酰胺后，乳腺腺癌和纤维腺瘤的总发病率均显著增加。高剂量组男性和女性以及低剂量组女性甲状腺滤泡细胞腺瘤和腺癌发生率均显著升高（p < 0.001）。在之前的丙烯酰胺致癌性研究中观察到的发病率增加的各种其他肿瘤类型（即合并中枢神经胶质肿瘤、口腔乳头状瘤、阴蒂腺瘤和子宫腺癌）在本研究中未观察到发病率增加。这项研究证实了先前描述的丙烯酰胺诱导甲状腺和乳腺良性肿瘤以及睾丸间皮瘤。通过使用大量动物和不平衡的研究设计，本研究表明丙烯酰胺不会诱导神经胶质瘤，并证明对阴囊间皮瘤的不可观察效应水平为0.5 mg/kg。研究还表明，乳腺肿瘤发病率的增加再次处于历史控制范围内。(C) 1995年毒理学学会。
A lifetime oncogenicity study in Fischer 344 rats was conducted to accurately characterize the carcinogenic potency of acrylamide. Acrylamide was administered in drinking water throughout the 106-week study at concentrations required to provide a dose of 0, 0.1, 0.5, or 2.0 mg/kg/day to males or 0, 1.0, or 3.0 mg/kg/day to females. Complete necropsy and gross pathology examinations were performed on all study animals. Histopathology examinations were conducted on selected tissues of all high-dose and control animals. Selected tissues from intermediate and low-dose groups were subjected to histopathological examinations as required to clarify high- and control-dose group observations. There was no visual observation of neurotoxicity in any study animal but sciatic nerve degeneration was observed in the male and female high-dose groups. Increased mortality related to acrylamide was observed in the high-dose male group from Month 17 to the end of the study and in the high-dose females during Month 24. Mesotheliomas of the testicular tunic were significantly increased in the high-dose male group. The combined incidence of mammary gland adenocarcinomas and fibroadenomas was significantly increased in both acrylamide-dosed female groups. Males and females in the high-dose groups as well as females of the low-dose group had significantly (p < 0.001) increased thyroid follicular cell adenomas and adenocarcinomas. A variety of other tumor types observed with increased incidence in a previous acrylamide oncogenicity study (i.e., combined CNS glial neoplasms, papillomas of the oral cavity, adenomas of the clitoral gland, and uterine adenocarcinomas) were not observed to be present at increased incidence in this study. This study confirms previously described acrylamide induction of benign tumors of the thyroid and mammary glands as well as mesotheliomas of the testis. By using a larger number of animals with an unbalanced study design, this study showed that acrylamide did not induce glial tumors and demonstrated that the no-observable-effect level for scrotal mesotheliomas is 0.5 mg/kg. It also demonstrated that the increased incidence of mammary tumors was again within historical control ranges. (C) 1995 Society of Toxicology.