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[静脉注射3,3-二乙基-1-甲基-1-亚硝基脲(DEMNU)对大鼠的产前和产后致癌作用]

[The pre- and postnatal carcinogenic effect of 3,3-diethyl-1-methyl-1-nitrosourea (DEMNU) in rats following intravenous application].

作者信息

Wagner U, Schreiber D, Thust R, Schneider M

机构信息

Institut für Pathologische Anatomie der Medizinischen Akademie Erfurt, DDR.

出版信息

Arch Geschwulstforsch. 1990;60(3):179-86.

PMID:2369280
Abstract

The pre- and postnatal administration of DEMNU induces a high frequency of tumors when applied via the intravenous route, and the latency periods show a dose dependence (table I). Tumors of the brain, spinal cord and cranial nerves clearly predominate. Furthermore, a large number of neoplasms of kidney, heart and soft tissue was observed (table II). As DEMNU is per se a very stable compound, it is suggested that this agent is metabolized by monooxygenases. 3-Ethyl-1-methyl-1-nitrosourea should be formed as an intermediate product via this pathway, which is relatively stable and might explain the mainly neurotropic carcinogenicity of DEMNU. Species differences in the carcinogenicity of trialkyl-nitrosoureas and the mode of metabolic activation are discussed.

摘要

当通过静脉途径给药时,DEMNU的产前和产后给药会诱发高频率的肿瘤,潜伏期呈剂量依赖性(表I)。脑、脊髓和颅神经的肿瘤明显占主导地位。此外,还观察到大量肾脏、心脏和软组织的肿瘤(表II)。由于DEMNU本身是一种非常稳定的化合物,因此推测该药剂由单加氧酶代谢。通过该途径应形成3-乙基-1-甲基-1-亚硝基脲作为中间产物,该中间产物相对稳定,这可能解释了DEMNU主要的神经嗜性致癌性。讨论了三烷基亚硝基脲致癌性的种属差异和代谢活化方式。

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