动物造模,药效评价,脑肿瘤 z-bio 2024-09-03 408

　　[Modeling mechanism] Injecting some chemical carcinogens into different parts of animals in different ways to induce tumors, but the incidence, type, and location of tumors induced by carcinogens vary with their dosage, animal age, strain, and physiological state (such as pregnancy and malnutrition). Chemical carcinogenicity refers to the process in which chemicals cause or induce the deterioration of normal cells and the development of tumors. Chemicals with such effects are called chemical carcinogens. Chemical carcinogenicity is generally a chronic process that triggers tumors after prolonged exposure to carcinogens. These substances may not immediately pose a threat to the body and only develop into tumors after a long incubation period.

　　In 1939, Seliman et al. injected methylcholanthrene (MC) into the brain tissue of 20 mice to induce brain tumors, most of which were glioblastoma and meningeal sarcoma. In the 1970s, a synthetic carcinogen N-nitrosourea and its derivative ethylnitrosourea (ENU) began to be widely used in the induction of brain tumors. For example, injecting 10mg/kg ENU into the brain of BD mice resulted in a total injection of 250mg/kg, causing tumors in various organs. Nine cases occurred in the hematopoietic system, and four cases occurred in the brain, small intestine, spinal cord, breast, and uterus. Vaccination of pregnant mice with 20-80mg/kg ENU mainly leads to the development of reproductive tract tumors, indicating that ENU is more likely to cause reproductive tract tumors during pregnancy. After administering ENU to pregnant mice, tumors can be transmitted to offspring through the placenta. ENU is suitable for inducing central nervous system tumors in the placenta, as small doses of carcinogens can induce a high incidence of neurological tumors in offspring of pregnant mice. For example, after intravenous injection of 50mg/kg ENU into 20 day pregnant Sprague Dawley rats, 25 generations were propagated, and each generation produced neurological tumors, resulting in a total of 102 cases of neurological tumors and 7 cases of non neurological tumors. After inoculation with carcinogens, the survival time of mice ranged from 85 to 346 days. Classification of tumors revealed 32 cases of oligodendroglioma, 4 cases of astrocytoma, 19 cases of mixed glioblastoma, 5 cases of interstitial glioblastoma, 4 cases of neurovascular ependymoma, 10 cases of ependymoma, 1 case of meningioma, and 27 cases of schwannoma. This study indicates that placental injection of ENU carcinogens has the advantages of successful induction, minimal age difference, and tumor diversity, providing sufficient sources for the study of neurogenic tumors.

　　The characteristic of this model is that brain tumors induced by carcinogens have significant differences in location, type, induction time, malignancy, and injection dosage. For example, after inoculating BDIX mice with 5-80mg/kg ENU for 1, 10, and 30 days, it was found that the incidence of neuroma in 1-day-old mice was higher than that in aged mice, indicating that the carcinogenic effect of young mice was greater than that of adult mice. After inoculating BDIX mice with different concentrations of ENU, it was found that 20-80mg/kg ENU did not produce or had a small amount of central system tumors. When the inoculation concentration reached 70 and 80mg/kg, the incidence of central system tumors increased to 20%. When the inoculation amount increased to 140mG/kg and 200mg/kg, the incidence of neurogenic tumors was 45% and 60%, respectively. This indicates that the induction rate of tumors is related to the dosage of carcinogens administered.

　　Model evaluation and application: Placental injection of carcinogenic nitrosamines such as ENU has the advantages of successful induction, small age difference, and tumor diversity, providing sufficient sources for research, vaccination, transplantation, clone analysis, and other studies of neurogenic tumors.