子宫内砷暴露与 Tg.AC 小鼠成年期非表皮增殖反应。
Arsenic exposure in utero and nonepidermal proliferative response in adulthood in Tg.AC mice.
机构信息
National Cancer Institute at NIEHS, Research Triangle Park, NC 27709, USA.
出版信息
Int J Toxicol. 2010 May-Jun;29(3):291-6. doi: 10.1177/1091581810362804.
Abstract
To expand our knowledge on the transplacental carcinogenic potential of inorganic arsenic, pregnant Tg.AC mice received drinking water with 0, 42.5, or 85 ppm arsenite from gestation day 8 to 18. After birth, groups (n = 25) of offspring received topical 12-O-tetradecanoyl phorbol-13-acetate (TPA) (2 microg twice a week) for 36 weeks and were killed; nonskin tumors were assessed. Arsenic increased adrenal cortical adenomas (ACAs; 25%-29%) compared with control (0%) independent of TPA in all male groups. Arsenic increased urinary bladder (UB) hyperplasia in males, but only with TPA. Arsenic induced ACAs in all female groups (control 0%; arsenic 17%-26%). Arsenic-treated females had UB hyperplasia in most groups (control 0%; arsenic 26%-32%), with 2 UB papillomas. All arsenic-treated females had uterine hyperplasia (26%-40%; control 4%) independent of TPA, and 3 had uterine tumors. Thus, arsenic in utero rapidly induces ACAs and uterine and UB preneoplasias in Tg.AC mice, showing transplacental carcinogenic potential in yet another strain of mice.
摘要
为了扩大我们对无机砷的胎盘致癌潜力的认识，妊娠 Tg.AC 小鼠从妊娠第 8 天到第 18 天接受含有 0、42.5 或 85ppm 亚砷酸盐的饮用水。出生后，将 25 组（n=25）后代接受局部 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）（2μg，每周两次）36 周，并进行了处死；评估非皮肤肿瘤。无论 TPA 如何，砷均会导致雄性所有组的肾上腺皮质腺瘤（ACAs；25%-29%）增加，而对照组（0%）则无此情况。砷会导致雄性的膀胱（UB）增生，但仅在使用 TPA 时才会发生。砷会导致所有雌性组的 ACAs（对照组 0%；砷组 17%-26%）增加。砷处理的雌性在大多数组中（对照组 0%；砷组 26%-32%）都出现了 UB 增生，其中 2 个出现了膀胱乳头状瘤。所有接受砷处理的雌性均出现了子宫增生（26%-40%；对照组 4%），与 TPA 无关，其中 3 个出现了子宫肿瘤。因此，砷在子宫内迅速诱导 Tg.AC 小鼠的 ACAs 和子宫及 UB 癌前病变，在另一种小鼠品系中显示出胎盘致癌潜力。
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