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暴露于异硫氰酸烯丙酯的大鼠肝脏中缺乏尿苷二磷酸葡萄糖醛酸基转移酶(UDS)活性。

Lack of UDS activity in the livers of rats exposed to allylisothiocyanate.

作者信息

Bechtel D, Henderson L, Proudlock R

机构信息

CanTox U.S. Inc., Bridgewater, New Jersey, USA.

出版信息

Teratog Carcinog Mutagen. 1998;18(5):209-17. doi: 10.1002/(sici)1520-6866(1998)18:5<209::aid-tcm1>3.0.co;2-6.

DOI:10.1002/(sici)1520-6866(1998)18:5<209::aid-tcm1>3.0.co;2-6
PMID:9876010
Abstract

Allylisothiocyanate (AITC) has been evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the livers of male rats in vivo. Specific Pathogen Free outbred albino Hsd/Ola Sprague-Dawley rats were exposed by oral gavage to 37.5 or 125 mg/kg AITC in corn oil and hepatocytes assessed for UDS by autoradiography 2 and 14 h later. AITC did not induce UDS at either dose level at either time point. These data are consistent with all other evidence indicating that AITC does not act as a genotoxin in vivo, despite positive response in some in vitro screening assays. The reported occurrence of benign bladder papillomas in male rats but not female rats or mice of either sex is consistent with non-genotoxic action and may be attributed to chronic irritation of the bladder epithelium by AITC and its cysteine conjugate metabolite excreted by male rats in unusually concentrated form. It is concluded that the weight of evidence is insufficient to regard AITC as a genotoxin capable of human carcinogenicity.

摘要

已对异硫氰酸烯丙酯(AITC)在雄性大鼠肝脏中引发非程序性DNA合成(UDS)的能力进行了评估。将无特定病原体的远交白化Hsd/Ola Sprague-Dawley大鼠通过灌胃给予玉米油中37.5或125 mg/kg的AITC,并在2小时和14小时后通过放射自显影评估肝细胞的UDS。在任何一个时间点,两种剂量水平的AITC均未诱导UDS。这些数据与所有其他证据一致,表明AITC在体内不作为基因毒素起作用,尽管在一些体外筛选试验中有阳性反应。据报道,雄性大鼠而非雌性大鼠或两性小鼠中出现良性膀胱乳头状瘤,这与非基因毒性作用一致,可能归因于AITC及其雄性大鼠以异常浓缩形式排泄的半胱氨酸共轭代谢产物对膀胱上皮的慢性刺激。结论是,现有证据不足以将AITC视为具有人类致癌性的基因毒素。

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