The occurrence of trigeminal nerve tumors (TNTs) induced by neonatal administration of N-ethyl-N-nitrosourea (ENU) in WF × LE F1 (F1 rats was studied with special reference to sex difference, effect of gonadectomy and estradiol (E2) administration. Experimental groups 1–6 were treated with 40 mg ENU/kg of body weight neonatally. They consisted of male, female, castrated male, ovariectomized female, E2 pellet (0.1 mg, s.c.) supplemented and gonadectomized male and female rats respectively. Rats of groups 7–12 served as the respective controls without ENU. All the rats were killed at 8 months of age. Levels of serum E2 and E2 receptor (ER) of the TNTs were also examined. It was noted that the incidence of TNT was higher in males (79%) than in females (48%, P < 0.05) and did not change by castration in males (91%) but increased in ovariectomized female rats (74%, P < 0.05). Administration of E2 followed by gonadectomy inhibited the occurrence of TNTs in male rats (59%) but not in female rats (60%). No TNT was observed in any control groups. Kidney tumors were the second most frequent tumors next to nervous system tumors in the present experiment. The incidence of kidney tumors was much higher in females (38%) than in males (4%, P < 0.05) and decreased by ovariectomy, whereas it increased in male rats by E2 administration. ER levels of TNTs and trigeminal nerve tissue were < 1 fmol/mg protein. These results suggest that in rats treated with ENU neonatally, E2 has an inhibitory effect on the induction of TNTs but may not be regulated through ER. E2 also shows a promoting effect on kidney tumorigenesis.
A genetic analysis was done on the induction of trigeminal schwannomas by N-ethyl-N-nitrosourea [(ENU) CAS: 759-73-9] in susceptible LE rats, resistant WF rats, and their F1, F2, and reciprocal backcross hybrids. Both sexes of all strains were given a neonatal sc injection of 40 mg ENU/kg body weight and were sacrificed at 6 months after treatment. Many neurogenic tumors were induced in the central nervous system of all strains of rats. However, the incidence of trigeminal schwannomas in LE rats was 93% in males and 86% in females, whereas in WF rats the incidence was 24% in males and 20% in females. F1 and F2 hybrids showed an intermediate susceptibility (62 and 82% in F1 males, 79 and 86% in F2 males, 26 and 38% in F1 females, and 65 and 77% in F2 females). The incidence in hybrids backcrossed to LE was high (90 and 100% in males and 77 and 83% in females), and the incidence in hybrids backcrossed to WF was low (35 and 38% in males and 11 and 7% in females). The findings suggest that susceptibility to the induction of trigeminal schwannomas by ENU does not result from the expression of genes that are simple dominant or recessive genes. A genetic model involving three independently segregating loci may explain the experimental results. In all strains of rats, particularly the F1 hybrids, males were more susceptible than females to the induction of trigeminal schwannomas by ENU.
The abilities of sn -1,2-didecanoylglycerol ( sn -1,2-DDG) to induce epidermal ornithinedecarboxylase (ODC) activity and epidermal hyperplasia were tested using SENCAR, DBA/2 and C57BL/6 mice. Following a single application of 5000 nmol of sn -1,2-DDG, ODC activity reached a maximum at 4 h after treatment with a peak activity of 6.03 nmol CO 2 /6mg protein/60 min in C57BL/6, 1.50 in SENCAR and 0.73 in DBA/2, respectively. The time course and magnitude for induction of ODC activity after multiple treatments was very similar to that after a single application in these three mouse lines. Interestingly, the induced ODC activityin C57BL/6 was always higher than that in SENCAR and DBA/2 mouse epidermis regardless of the treatment protocol. Induction of hyperplasia and dark basal keratinocytes (DCs) and changes in the labeling index (LI) of basal keratinocytes in DBA/2 and C57BL/6 mice following treatment with sn -1,2-DDG were investigated. Multiple treatments (twice weekly for 2 weeks) of 5000 nmol sn -1,2-DDG did not induce substantial increases inepidermal thickness or DCs 24 or 48 h after the last treatment. In contrast, TPA induced a marked increase in epidermal thickness in DBA/2 rather than CS7BL/6 and a considerably higher induction of DCs in DBA/2 (37.3 ± 2.2%) than in CS7BL/6 (9.6 ± 2.5%) 48 h after the last treatment. The LIs after topical application of sn -1,2-DDG were elevated at 24 h, but returned to basal levels by 48 h in both strains, whereas TPA treatment significantly elevated the LI In both strains at 48 h after the last application. In addition, the effects of various doses and frequencies of application of sn -1,2-DDG were investigated using SENCAR mice. Highdoses (20 000 nmol) or more frequent applications (5000 nmol once daily for 7 days) of sn -1,2-DDG still produced only weak hyperplasia. These results suggest that the induction of epidermal ODC activity can be dissociated from the induction of epidermal hyperplasia and may provide an explanation for the lack of complete promoting activity presently observed with membrane permeable diacylglycerol derivatives.
Three cases of rectal stricture, 47 aged male, 52 aged female and 40 aged male, were diagnosed as rectal carcinoma. One stage abdomino-perineal resection was done in one case and two stage operation in others. Their histologic findings showed nonspecific chronic inflammation and there were no malignancies. Differentiation from ulcerative colitis or venereal lymphogranuloma could not be cleared because of some erosion of mucous membrane, fibric hyperplasia of the wall and infiltration of small round cells and no performance of Frei test.
The authors reported a case of the spinal tumor which was considered to be a primary intraspinal medulloblastoma.27 year-old male was admitted with the complaints of paraplesia and myelographic examination showed the space occupying lesion at the 4th & 5th thoracic vertebrae.Twice operations were carried out due to the recurrence in the same location.Histologically the tumor was revealed medulloblastoma.11 months after the onset, the symptoms is completely relieved and there is no evidence of the intracranial involvement.
N-methyl-N-nitrosourea (MNU) 50mg/kg b.w. was administered to 50-day-old LE, WFN and F1A (WFN×LE) rats maintained in our laboratory and after 24 weeks of MNU treatment they were sacrificed and served for pathological study. The developed tumors were mainly kidney, mammary tumors, and leukemia. Kidney tumor was histologically considered to be of mesenchymal origin similating a fibrosarcoma, and mammary tumors were tubular, papillary or compact type adenocarcinomas and fibromas. The mesenchymal tumors of kidney was observed only in WFN rats and its incidence was as high as 46.7%. DNA synthesis of the kidney at 50 days was examined. Bromodeoxyuridine (BrDU) 20mg/200g b.w. was injected into peritoneal cavity in LE, WFN, F1A rats and after 60min they were sacrificed and incorporation of BrDU in the kidney cells was examined by anti-BrDU monoclonal antibody and ABC method. The mean incorporated cell numbers in one kidney by 10 fields were LE 4.3±3.4, WFN 16.3±7.3, F1A 2.5±2.6. BrDU uptake in WFN rat kidney was significantly (P<0.01) elevated. This finding well correlated with the occurrence of kidney tumor.
Morphological and immunohistochemical studies of cerebellar tumor induction with neonatal administration of N-ethyl-N-nitrosourea (ENU) were conducted in four strains of rats and their hybrids, i.e., noninbred Wistar, Fischer (F344), Long-Evans, Wistar/Furth, and hybrids of Long-Evans and Wistar/Furth. Neonatal s.c. injection of 40 mg ENU/kg body weight produced 53 cerebellar tumors in 46 (8.4%) rats among 550 animals. There was no sex difference in the incidence (male = 9.6%; female = 7.0%). Histological examination showed that most of the tumors (83%) were oligodendrogliomas and the neoplastic cells were positively stained immunohistochemically with anti-Leu-7 monoclonal antibody. In examining the location of cerebellar tumors, 22 (42%) were located in the vermis, 11 (21%) in the hemisphere, 9 (17%) in the flocculus, 6 (11%) in the peduncle, and 5 (9%) in other sites. When their origins were examined in relation to their location to the internal granular layer of the cerebellum, 40 (75%) tumors were found just under the internal granular layer (subcortical region) and 9 (17%) in the white matter or cerebellar nuclei. Only 2 (4%) subependymal tumors were observed. Ontogenic study of the rat cerebellum revealed the presence of an aggregation of primitive glial cells in the subcortical region during the neonatal period, and the [3H]thymidine pulse-labeling index of these cells was 13.7%. Electron microscopic study showed the primitive nature of these cells and they reacted positively with anti-Leu-7 monoclonal antibody. These results indicate that cerebellar tumors are induced in an appreciable incidence with neonatal injection of ENU in rats and that cerebellar target cells in the subcortical region are present after ENU carcinogenesis.
In osteoarthritis (OA), synovial pathology may be induced by proteins released from degenerated cartilage. This study was conducted to identify the proteins released from OA cartilage. OA cartilage was obtained from OA knees at macroscopically preserved areas (PRES) and degenerated areas (DEG), while control cartilage (CONT) was collected from non-arthritic knees. Released proteins were obtained from these cartilage samples by repeatedly applying compressive loading, which simulated loading on cartilage in vivo. The released proteins were analyzed comprehensively by antibody array analyses and a quantitative proteomic analysis. For several proteins, the exact amounts released were determined by Luminex assays. The amount of active TGF-β that was released was determined by an assay using genetically-engineered HEK cells. The results of the antibody array and proteomic analyses revealed that various biologically active proteins are released from OA cartilage, particularly from DEG, by loading. The Luminex assay confirmed that several alarmins, complement proteins C3a and C5a, and several angiogenic proteins including FGF-1, FGF-2 and VEGF-A were released in greater amounts from DEG than from CONT. The HEK cell assay indicated that active TGF-β was released from DEG at biologically significant levels. These findings may be helpful in understanding the pathology of OA.
