Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.
Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.
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DOI：
10.1289/ehp.6655
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发表时间：
2004-04
影响因子：
10.4
通讯作者：
Rossman TG
中科院分区：
文献类型：
--
作者：
Burns FJ;Uddin AN;Wu F;Nádas A;Rossman TG
本研究旨在在小鼠皮肤模型中建立膳食亚砷酸钠作为共同致癌物与紫外线辐射 (UVR) 的剂量反应关系形式。无毛小鼠（品系 Skh1）从 21 日龄开始，以浓度为 0.0、1.25、2.5、5.0 和 10 mg/L 的饮用水连续喂食亚砷酸钠。 42 天时，每周对背部皮肤进行 3 次太阳光谱 UVR 照射，每次照射强度为 1.0 kJ/m2，直到 182 天实验结束。未经治疗的小鼠和仅喂食亚砷酸的小鼠没有产生肿瘤。其余组中共有 322 例发生局部浸润性鳞状细胞癌。仅暴露于 UVR 的小鼠在 182 天时的癌症产量为 2.4 +/- 0.5 个癌症/小鼠。膳食亚砷酸盐显着增强了 UVR 诱导的癌症产量，其线性模式与 5.0 mg/L 亚砷酸盐高达 11.1 +/- 1.0 个癌症/小鼠的峰值一致，代表峰值增强比率为 4.63 +/- 1.05。在 10.0 mg/L 亚砷酸盐浓度下，每只小鼠的癌症数量下降了 6.8 +/- 0.8 个。新癌症发病率与初始无癌间隔后开始的时间呈现出一致的线性依赖性，范围在 88 至 95 天之间。单独的亚砷酸盐和单独的UVR都会使表皮增生升高，并且比组合暴露的累加作用更大，癌症的生长速度也是如此。这些结果证明了新的动物模型可用于研究膳食亚砷酸盐对暴露于紫外线的皮肤的致癌作用，并应有助于了解如何利用动物数据来评估暴露于致癌物和癌症增强剂混合物的组织中的人类癌症风险。
The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experiment ended at 182 days. Untreated mice and mice fed only arsenite developed no tumors. In the remaining groups a total of 322 locally invasive squamous carcinomas occurred. The carcinoma yield in mice exposed only to UVR was 2.4 +/- 0.5 cancers/mouse at 182 days. Dietary arsenite markedly enhanced the UVR-induced cancer yield in a pattern consistent with linearity up to a peak of 11.1 +/- 1.0 cancers/mouse at 5.0 mg/L arsenite, representing a peak enhancement ratio of 4.63 +/- 1.05. A decline occurred to 6.8 +/- 0.8 cancers/mouse at 10.0 mg/L arsenite. New cancer rates exhibited a consistent-with-linear dependence on time beginning after initial cancer-free intervals ranging between 88 and 95 days. Epidermal hyperplasia was elevated by arsenite alone and UVR alone and was greater than additive for the combined exposures as were growth rates of the cancers. These results demonstrate the usefulness of a new animal model for studying the carcinogenic action of dietary arsenite on skin exposed to UVR and should contribute to understanding how to make use of animal data for assessment of human cancer risks in tissues exposed to mixtures of carcinogens and cancer-enhancing agents.
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影响因子：
7.7
作者：
Mazumder, DNG;Haque, R;Smith, AH
通讯作者：
Smith, AH
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.95.14.8103
发表时间：
1998-07-07
影响因子：
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通讯作者：
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通讯作者：
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