Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice
Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice
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DOI：
10.1016/s0041-008x(02)00022-4
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发表时间：
2003-01-01
影响因子：
3.8
通讯作者：
Diwan, BA
中科院分区：
文献类型：
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作者：
Waalkes, MP;Ward, JM;Diwan, BA
砷是一种已知的人类致癌物质，但发展无机砷致癌的啮齿动物模型一直存在问题。由于妊娠期通常是化学致癌的高敏感期，我们使用无机砷对小鼠进行了经胎盘致癌研究，从怀孕第8天到第18天，对10组怀孕的C3H小鼠分别饮用0(对照)、42.5和85ppm亚砷酸盐(NaAsO2)的饮用水。这些剂量的耐受性很好，怀孕期间和出生后后代的体重没有减轻。允许母猪分娩，并在4周时断奶，然后根据母亲的暴露水平将其分成不同的性别组(25只)。后代没有接受额外的砷治疗。该研究在男性身上持续了74周，在女性身上持续了90周。对所有小鼠进行完整的尸检，并在光学显微镜下盲法检查组织。在雄性后代中，肝细胞癌的发病率以与剂量相关的方式显著增加(对照组，12%；42.5ppm，38%；85ppm，61%)和肝脏肿瘤的多样性(每肝肿瘤；在85ppm时是对照组的5.6倍)，在男性中，肾上腺肿瘤的发病率和多样性也随着剂量的增加而增加。在雌性后代身上。卵巢肿瘤发病率(对照，8%；42.5ppm，26ppm，85ppm，38%)和肺癌发病率(对照，0%，42.5ppm，4%；85ppm，21%)随剂量增加而增加。砷暴露还增加了子宫和输卵管增生性病变的发生率。这些结果表明，口服无机砷作为一种单一因素，可以在啮齿动物体内诱导肿瘤形成，并在小鼠中确立无机砷是一种完全的胎盘致癌物。无机砷致癌啮齿动物模型的建立对明确这种常见环境致癌物质的作用机制具有重要意义。(C)2003爱思唯尔科学(美国)，版权所有。
Arsenic is a known human carcinogen, but development of rodent models of inorganic arsenic carcinogenesis has been problematic. Since gestation is often a period of high sensitivity to chemical carcinogenesis, we performed a transplacental carcinogenicity study in mice using inorganic arsenic, Groups (n = 10) of pregnant C3H mice were given drinking water containing sodium arsenite (NaAsO2) at 0 (control), 42.5, and 85 ppm arsenite ad libitum from day 8 to 18 of gestation. These doses were well tolerated and body weights of the dams during gestation and of the offspring subsequent to birth were not reduced. Darns were allowed to give birth, and offspring were weaned at 4 weeks and then put into separate gender-based groups (it = 25) according to maternal exposure level. The offspring received no additional arsenic treatment. The study lasted 74 weeks in males and 90 weeks in females. A complete necropsy was performed on all mice and tissues were examined by light microscopy in a blind fashion. In male offspring, there was a marked increase in hepatocellular carcinoma incidence in a dose-related fashion (control, 12%; 42.5 ppm, 38%; 85 ppm, 61%) and in liver tumor multiplicity (tumors per liver; 5.6-fold over control at 85 ppm), In males, there was also a dose-related increase in adrenal tumor incidence and multiplicity. In female offspring. dose-related increases Occurred in ovarian tumor incidence (control, 8%; 42.5 ppm, 26% 85 ppm, 38%) and lung carcinoma incidence (control, 0% 42.5 ppm, 4%; 85 ppm, 21%). Arsenic exposure also increased the incidence of proliferative lesions of the uterus and oviduct. These results demonstrate that oral inorganic arsenic exposure, as a single agent, can induce tumor formation in rodents and establishes inorganic arsenic as a complete transplacental carcinogen in mice. The development of this rodent model of inorganic arsenic carcinogenesis has important implications in defining the mechanism of action for this common environmental carcinogen. (C) 2003 Elsevier Science (USA), All rights reserved.