Exposure to N-nitroso compounds (NOCs) during pregnancy has been associated with an increase in brain tumors in the progeny. This study investigated the brain tumorigenic effect of N-ethyl N-nitrosourea (ENU) after differential exposure of rats during pregnancy.

Sprague Dawley rats were exposed to a single dose of ENU (80 mg/kg) in three different circumstances: 1) at first, second or third week of gestation; 2) at the 15th embryonic day (E15) in consecutive litters and 3) at E15 in three successive generations. Location and characterization of the offspring's brain tumors were performed by magnetic resonance imaging and histopathological studies. Finally, tumor incidence and latency and the animals' survival were recorded.

ENU-exposure in the last two weeks of pregnancy induced intracranial tumors in over 70% of the offspring rats, these being mainly gliomas with some peripheral nerve sheath tumors (PNSTs). Tumors appeared in young adults; glioma-like small multifocal neoplasias converged on large glioblastomas in senescence and PNSTs in the sheath of the trigeminal nerve, extending to cover the brain convexity. ENU-exposure at E15 in subsequent pregnancies lead to an increase in glioma and PNST incidence. However, consecutive generational ENU-exposure (E15) decreased the animals' survival due to an early onset of both types of tumors. Moreover, PNST presented an inheritable component because progeny, which were not themselves exposed to ENU but whose progenitors were, developed PNSTs.

Our results suggest that repeated exposure to ENU later in pregnancy and in successive generations favours the development of intracranial gliomas and PNSTs in the offspring.

怀孕期间接触 N-亚硝基化合物 (NOC) 与后代脑肿瘤的增加有关。本研究调查了在怀孕期间大鼠不同暴露后 N-乙基 N-亚硝基脲 (ENU) 的脑肿瘤发生作用。

Sprague Dawley 大鼠在三种不同情况下暴露于单剂量 ENU (80 mg/kg)： 1) 在妊娠第一、第二或第三周；2) 在第 15 个胚胎日 (E15) 连续产仔和 3) 在 E15 连续三代。通过磁共振成像和组织病理学研究对后代脑肿瘤进行定位和表征。最后，记录肿瘤发生率和潜伏期以及动物的存活率。

妊娠最后两周的 ENU 暴露在超过 70% 的后代大鼠中诱发颅内肿瘤，这些主要是神经胶质瘤和一些周围神经鞘瘤 (PNST)。肿瘤出现在年轻人身上；胶质瘤样小的多灶性肿瘤在衰老的大胶质母细胞瘤和三叉神经鞘中的 PNST 上汇聚，延伸至覆盖大脑凸面。随后怀孕中 E15 的 ENU 暴露导致胶质瘤和 PNST 发病率增加。然而，由于这两种肿瘤的早期发病，连续几代 ENU 暴露 (E15) 降低了动物的存活率。此外，PNST 提供了一个可继承的组件，因为后代本身并未暴露于 ENU，但其祖先却开发了 PNST。

我们的研究结果表明，在妊娠后期和连续几代反复接触 ENU 有利于后代颅内神经胶质瘤和 PNST 的发展。