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青春期前接触丙烯酰胺 (AA) 对 F344 大鼠 N-甲基-N-亚硝脲 (MNU) 诱导的多器官致癌作用无修饰作用。

Lack of modifying effects of prepubertal exposure to acrylamide (AA) on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis in F344 rats.

机构信息

Division of Pathology, National Institute of Health Sciences, Tokyo.

出版信息

J Toxicol Sci. 2010 Feb;35(1):57-68. doi: 10.2131/jts.35.57.

Abstract

Acrylamide (AA) has been reported to be formed in fried and baked foods with various concentrations, and exposure levels to AA from cooked foods in children are estimated to be higher than those in adults. In order to evaluate the carcinogenicity of AA exposure during childhood, we conducted a medium-term carcinogenicity study with prepubertal administration of AA followed by treatments of a multi-organ-targeted genotoxic carcinogen and a promoting agent for thyroid carcinogenesis in rats. A total of 36 postpartum F344 rats were given drinking water containing AA at 0, 20, 40 or 80 ppm for 3 weeks during the lactation period, and their weaned offspring received the same AA-containing water for 3 more weeks. Offspring were then injected with N-methyl-N-nitrosourea (MNU; 40 mg/kg body weight, i.p.) once at week 7 after birth. Half the animals of the 0 and 40 ppm groups were additionally treated with the anti-thyroid agent sulfadimethoxine (SDM; 125 ppm) in the drinking water thereafter. Offspring were subjected to complete necropsy at week 50. All the major organs and macroscopic abnormalities were excised and examined histopathologically. There was no significant difference in the incidences of hyperplastic and neoplastic lesions in the target organs of AA and/or MNU, such as the brain, spinal cord, pituitary gland, thyroid, adrenal glands, uterus, mammary glands, clitoral gland and tunica vaginalis. In conclusion, no significant modifying actions of AA on MNU-induced multi-organ carcinogenesis were exhibited in any organs of rats when exposed prepubertally under the present experimental conditions.

摘要

丙烯酰胺(AA)已被报道在各种浓度的油炸和烘焙食品中形成,儿童从烹饪食品中接触 AA 的水平估计高于成人。为了评估儿童期接触 AA 的致癌性,我们进行了一项中期致癌性研究,即在青春期前给予 AA 处理,然后用多器官靶向遗传致癌物和甲状腺致癌促进剂对大鼠进行处理。共有 36 只产后 F344 大鼠在哺乳期给予含有 0、20、40 或 80ppmAA 的饮用水 3 周,然后其断奶后代再饮用相同的含 AA 水 3 周。然后,在出生后第 7 周,对后代单次腹腔内注射 N-甲基-N-亚硝脲(MNU;40mg/kg 体重)。0 和 40ppm 组的一半动物随后在饮用水中添加抗甲状腺剂磺胺二甲氧嘧啶(SDM;125ppm)。在第 50 周对后代进行全面尸检。切除所有主要器官和肉眼可见的异常,并进行组织病理学检查。AA 和/或 MNU 的靶器官(如脑、脊髓、垂体、甲状腺、肾上腺、子宫、乳腺、阴蒂和阴道膜)的增生和肿瘤病变的发生率在 AA 组之间没有显著差异。因此,在本实验条件下,青春期前暴露于 AA 下,AA 对 MNU 诱导的多器官致癌作用没有明显的修饰作用。

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