动物造模,药效评价,脑肿瘤 z-bio 2024-09-04 615

　　Vazquez Lopez first discovered that viruses can induce tumors, but the pathogenesis has not been fully elucidated. The possible mechanism is that viruses themselves have replication and genetic functions. After infecting cells, they release genetic material that integrates into the host cell genome, causing cancer. In addition, some viruses have oncogenes in their own genes, which can encode proteins to promote host cell cancer. Currently, there are two types of viruses used to cause brain tumors: DNA viruses (such as adenovirus) and RNA viruses (such as Rous sarcoma virus).

　　Viruses are widely used as carcinogens due to their short incubation period for tumor formation and relatively high rate of brain tumor formation, with a wide range of species.

　　1. Robert F et al. inoculated 100000 FFU of virus into the brain of aged rats. After a 3-month incubation period, 24 out of 25 inoculated rats developed primary brain tumors: glioblastoma accounted for 60%, sarcoma accounted for 31%, and glioblastoma accounted for 9%.

　　In 1964, Rabotti induced the development of brain tumors in neonatal hamsters using the Schmidt Ruppin strain of Rous sarcoma viruses (RSV) from chickens, mainly stromal gliomas and sarcomas. Simian vacuolar virus 40 (SV40) can induce ependymoma and choroid plexus tumors in hamsters. Eddy et al. induced ependymoma production by inoculating SV40 virus into the brain of newborn hamsters. After inoculating the human JC virus into the brain of hamsters, it can cause ependymoma, pineoblastoma, extracranial neuroblastoma, and neuroblastoma. The administration of SV40 virus into the brain of newborn hamsters induces tumor formation, and the tumorigenic effect of the virus is proportional to the amount administered. One year after intracranial inoculation of bovine papillomavirus in hamsters, meningiomas, fibromas, and fibrosarcomas were found to occur. PV virus isolated from human brain tissue with progressive multifocal leukoencephalopathy can induce various brain tumors in newborn hamsters, such as cerebellar medulloblastoma, thalamic glioma, ependymoma, meningioma, and pineal gland tumor.

　　3. The probability of inducing canine brain tumors with RSV is also relatively high. When tumors are classified by electron microscopy, gliomas are dominant, and the site of inoculation is the dominant factor in inducing brain tumor types. When inoculated in the deep layer of the ventricular membrane, only astrocytes and glioblastomas are induced. When inoculated on the surface of the cortex or in the vermis of the cerebellum, only sarcomas are induced. Bigner et al. injected concentrated Rous sarcoma virus (100 μ l) into the brain of a newborn dog, and after a latent period, all of them developed gliomas or sarcomas.

      4.After the monkey human JC virus is inoculated into the monkey's brain tissue, primary central nervous system tumors such as malignant gliomas or mixed tumors of gliomas and neuronal cell tumors can be detected in the monkey's brain within 16-25 months. Tabuchi et al. inoculated fibroblasts infected with Rous virus into the right frontal lobe of monkeys, and 73% of monkeys developed tumors, mainly sarcomas.

　　The type of induced tumor depends on the site of inoculation and the age of the animal. Sarcoma is more likely to occur in the convex surface of the brain or the vermis of the cerebellum, while glioma is more likely to occur in the subendoventricular membrane. Newborn animals are more susceptible than adult animals.

　　From the established virus induced brain tumor models, it can be seen that inbred animals are prone to mimic the biological characteristics of human brain tumors. Virus induced brain tumors can serve as both a model for exploring the pathogenesis of brain tumors and a source for studying treatment models. Brain tumors can be continuously passaged in the same animal species and cloned to create biologically stable models. However, their tumorigenic cycles vary greatly, and the nature of tumor induction varies greatly. Moreover, viruses are not suitable for preservation and have a certain harmful effect on humans, which limits their application.