Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
In Vivo. 2011 Jan-Feb;25(1):11-22.
N-Methyl-N-nitrosourea (MNU) is a direct-acting alkylating agent that interacts with DNA. Accumulation of mutations may enhance cancer risk in target organs or cause cell death in susceptible tissues or cells when excessive DNA damage is not repaired. MNU targets various organs in a variety of animal species. MNU-induced carcinogenesis can be used as organ-specific animal models for human cancer, and MNU has been most extensively utilized for the induction of mammary cancer in rats. MNU-induced rat mammary tumors possess many similarities to those of human breast cancer, and the model is utilized for screening cancer modulators. MNU-induced cell disruption is also seen in several organs and tissues, especially when MNU is applied before maturity. However, photoreceptor cells in adults are highly sensitive to MNU, which causes cell death due to apoptosis. MNU-induced photoreceptor apoptosis mimics human retinitis pigmentosa and can be used for studies of therapeutic intervention. In this review, the targets of MNU in various animal species are described, and special emphasis is given to therapeutic trials against MNU-induced mammary cancer and retinal degeneration in animal models.
N-甲基-N-亚硝脲（MNU）是一种直接作用的烷化剂，可与 DNA 相互作用。当过量的 DNA 损伤未得到修复时，突变的积累可能会增加靶器官的癌症风险，或导致敏感组织或细胞死亡。MNU 可靶向多种动物物种的各种器官。MNU 诱导的致癌作用可作为针对人类癌症的特定器官动物模型，并且 MNU 已被广泛用于诱导大鼠的乳腺癌。MNU 诱导的大鼠乳腺癌与人类乳腺癌有许多相似之处，该模型用于筛选癌症调节剂。MNU 诱导的细胞破坏也可见于几种器官和组织中，尤其是在成熟前应用 MNU 时。然而，成年的感光细胞对 MNU 高度敏感，这会导致细胞凋亡引起的细胞死亡。MNU 诱导的感光细胞凋亡模拟了人类色素性视网膜炎，可以用于治疗干预的研究。在这篇综述中，描述了 MNU 在各种动物物种中的靶标，并特别强调了针对动物模型中 MNU 诱导的乳腺癌和视网膜变性的治疗试验。
