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雄性F344大鼠短期膳食丙烯酰胺暴露的毒理学效应

Toxicological effects of short-term dietary acrylamide exposure in male F344 rats.

作者信息

Raju Jayadev, Roberts Jennifer, Taylor Marnie, Patry Dominique, Chomyshyn Emily, Caldwell Don, Cooke Gerard, Mehta Rekha

机构信息

Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario, Canada.

Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch Health Canada, Ottawa, Ontario, Canada.

出版信息

Environ Toxicol Pharmacol. 2015 Jan;39(1):85-92. doi: 10.1016/j.etap.2014.11.009. Epub 2014 Nov 22.

Abstract

We recently reported that acrylamide, a known rodent and probable human carcinogen, does not increase the risk of azoxymethane (AOM)-induced rat colon precancerous lesions when administered through the diet. Here, we present toxicological data from non-AOM-injected rats. Briefly, male F344 rats were randomized into four dietary groups and received experimental diets based on AIN-93G formulation and containing acrylamide at 0 (control), 5, 10 or 50mg/kg diet (wt/wt) ad libitum for 10 weeks, after which they were killed and their blood collected for hematological and biochemical markers. Acrylamide at the higher doses (10 and 50mg/kg diet) significantly lowered (p<0.05) serum total high density lipoprotein and total testosterone and increased serum lipase in comparison to the control. Blood hematocrit values and lymphocyte counts were significantly lower (p<0.05) in the high dose acrylamide (50mg/kg diet) group compared to control, with a concomitant decrease in hemoglobin level, mean corpuscular volume and mean corpuscular hemoglobin. These results provide additional hazard characterization data and strengthen the notion that at high doses, acrylamide may involve systemic toxicity potentiating tumorigenesis in experimental animals. Further studies are required to understand the health effects of food-borne acrylamide, especially at the lower exposures typified by human diets.

摘要

我们最近报告称,已知的啮齿动物致癌物及可能的人类致癌物丙烯酰胺,经饮食给药时不会增加氧化偶氮甲烷(AOM)诱导的大鼠结肠癌前病变风险。在此,我们展示了未注射AOM的大鼠的毒理学数据。简要来说,雄性F344大鼠被随机分为四个饮食组,根据AIN-93G配方接受实验饮食,饮食中丙烯酰胺含量分别为0(对照组)、5、10或50mg/kg饮食(重量/重量),随意进食10周,之后处死大鼠并采集血液,检测血液学和生化指标。与对照组相比,高剂量(10和50mg/kg饮食)的丙烯酰胺显著降低了(p<0.05)血清总高密度脂蛋白和总睾酮水平,并增加了血清脂肪酶水平。与对照组相比,高剂量丙烯酰胺(50mg/kg饮食)组的血细胞比容值和淋巴细胞计数显著降低(p<0.05),同时血红蛋白水平、平均红细胞体积和平均红细胞血红蛋白含量也随之下降。这些结果提供了额外的危害特征数据,并强化了这样一种观念,即高剂量时,丙烯酰胺可能会引发全身毒性,增强实验动物的肿瘤发生。需要进一步研究以了解食物源性丙烯酰胺对健康的影响,尤其是以人类饮食中典型的低暴露水平的影响。

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