Classification of spontaneous brain tumors in rats

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Classification of spontaneous brain tumors in rats

Central Nervous System Neoplasms in the Rat (Solleveld HA, et al., 1991) 1. Tumors of Neuroepithelial Tissue A. Astrocytic and oligodendroglial tumors Astrocytoma Oligodendroglioma Mixed glioma (oligo-astrocytoma) Anaplastic glioma B. Ependymal and choroid plexus tumors Ependymoma Choroid plexus papilloma Choroid plexus carcinoma C. Pineal gland neoplasms Pinealoma Pineal gland carcinoma D. Neuronal and primitive bipotential precursor cell neoplasms Ganglioglioma Ganglioneuroma Medulloblastoma 2. Tumors of Nerve Sheath Cells Schwannoma (benign or malignant) 3. Tumors of Meninges and Related Tissues Meningioma Meningeal sarcoma Granular cell tumor Malignant melanoma 4. Primary Lymphomas Malignant reticulosis

Incidence of spontaneous brain tumors in NIBS

Incidence of Spontaneous Brain Tumors in F344 Rats in NIBS a Tumors Male Female Total n=2142 b n=2092 n=4234 Astrocytoma 11 (0.51) c 5 (0.24) 16 (0.38) Oligodendroglioma 9 (0.42) 6 (0.29) 15 (0.35) Ependymoma 2 (0.09) 0 (0) 2 (0.05) Medulloblastoma 1 (0.05) 1 (0.05) 2 (0.05) Meningioma 6 (0.28) 1 (0.05) 7 (0.17) Granular cell tumor 4 (0.19) 1 (0.05) 5 (0.12) Malignant reticulosis 1 (0.05) 0 (0) 1 (0.02) Total 34 (1.59) 14 (0.67) 48 (1.13) a: Surviving rats were examined at 109 weeks of age. b: Number of rats examined. c: Percentage.

Comparison of incidences of spontaneous brain tumors in several facilities

Incidences of Spontaneous Brain Tumors in Male F344 Rats in Seven Facilities Tumor Type NIBS a NCI b NTP c NIEHS d NIHS e IET f BRC g n=2142 h n=1794 n=1928 n=1335 n=296 n=960 n=696 Neuroglia Astrocytoma 11 (0.51) i 7 (0.39) 9 (0.47) 5 (0.37) 4 (1.35) 0 (0) 1 (0.14) Oligodendroglioma 9 (0.42) 0 (0) 2 (0.10) 5 (0.37) 1 (0.34) 0 (0) 0 (0) Glioma 0 (0) 4 (0.22) 2 (0.10) 1 (0.07) 0 (0) 3 (0.31) 2 (0.29) Ependymoma 0 (0) 2 (0.11) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Embryonal/undifferentiated cells Medulloblastoma 0 (0) 0 (0) 1 (0.05) 0 (0) 0 (0) 0 (0) 0 (0) Neuroblastoma 0 (0) 0 (0) 0 (0) 1 (0.07) 0 (0) 0 (0) 0 (0) Meninges Meningioma 10 (0.47) 0 (0) 2 (0.10) 1 (0.07) 0 (0) 1 (0.10) 0 (0) Granular cell tumor 0 (0) 0 (0) 4 (0.21) 3 (0.22) 0 (0) 1 (0.10) 0 (0) Miscellaneous Malignant reticulosis 1 (0.05) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Sarcoma 0 (0) 2 (0.11) 0 (0) 1 (0.07) 0 (0) 0 (0) 0 (0) Total 31 (1.45) 15 (0.84) 20 (1.04) 17 (1.27) 5 (1.69) 5 (0.52) 3 (0.43) a: Nippon Institute for Biological Science (2004). b: National Cancer Institute, Goodman DG et al. (1979). c: National Toxicology Program of NIEHS, Haseman JK et al. (1990). d: National Institute of Environmental Health Sciences, Hasemen JK et al. (1998). e: Natioanl Institute of Hygienic Science, Maekawa A et al. (1983). f: Institute of Environmental Toxicology, Maita K et al. (1987). g: Biosafety Research Centar, Foods, Drugs and Pesticides, Iwata H et al. (1991). h: Number of rats examined. i: Percentage.

Incidences of Spontaneous Brain Tumors in Female F344 Rats in Seven Facilities Tumor Type NIBS a NCI b NTP c NIEHS d NIHS e IET f BRC g n=2092 h n=1754 n=1969 n=1349 n=297 n=959 n=700 Neuroglia Astrocytoma 5 (0.24) i 3 (0.17) 18 (0.91) 4 (0.30) 2 (0.67) 0 (0) 1 (0.14) Oligodendroglioma 6 (0.29) 2 (0.11) 3 (0.15) 4 (0.30) 0 (0) 0 (0) 1 (0.14) Glioma 0 (0) 2 (0.11) 2 (0.10) 4 (0.30) 0 (0) 4 (0.42) 0 (0) Ependymoma 0 (0) 1 (0.06) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Embryonal/undifferentiated cells Medulloblastoma 1 (0.05) 0 (0) 1 (0.05) 0 (0) 0 (0) 0 (0) 0 (0) Meninges Meningioma 1 (0.05) 0 (0) 2 (0.10) 0 (0) 0 (0) 0 (0) 0 (0) Granular cell tumor 1 (0.05) 0 (0) 0 (0) 2 (0.15) 0 (0) 0 (0) 0 (0) Miscellaneous Malignant reticulosis 0 (0) 2 (0.11) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Total 14 (0.67) 10 (0.57) 26 (1.32) 14 (1.04) 2 (0.67) 4 (0.42) 2 (0.29) a: Nippon Institute for Biological Science (2004). b: National Cancer Institute, Goodman DG et al. (1979). c: National Toxicology Program of NIEHS, Haseman JK et al. (1990). d: National Institute of Environmental Health Sciences, Hasemen JK et al. (1998). e: Natioanl Institute of Hygienic Science, Maekawa A et al. (1983). f: Institute of Environmental Toxicology, Maita K et al. (1987). g: Biosafety Research Centar, Foods, Drugs and Pesticides, Iwata H et al. (1991). h: Number of rats examined. i: Percentage.

Incidences of Spontaneous Brain Tumors in F344 Rats in Seven Facilities Incidence (%) 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 Male Female NIBS NCI NTP NIEHS NIHS IET BRC

Summary of Spontaneous Brain Tumors in F344 Rats Incidence Sex ratio Tumor type : Very low : Male > Female : Various

Incidence of ENU-induced Preneoplastic and Neoplastic Brain Lesions in F344 Rats 20 weeks of age 32 weeks of age Lesions Male Female Total Male Female Total n=300 a n=300 n=600 n=300 n=300 n=600 Preneoplastic lesion Atypical hyperplasia of astroglia 34 (11.3) b 35 (11.7) 69 (11.5) 44 (14.7) 42 (14.0) 86 (14.3) Atypical hyperplasia of oligodendroglia 8 (2.7) 7 (2.3) 15 (2.5) 7 (2.3) 3 (1.0) 10 (1.7) Total 42 (14.0) 42 (14.0) 84 (14.0) 51 (17.0) 45 (15.0) 96 (16.0) Neoplastic lesion Astrocytoma 32 (10.7) 29 (9.7) 61 (10.2) 112 (37.3) 109 (36.3) 221 (36.8) Oligodendroglioma 8 (2.7) 4 (1.3) 12 (2.0) 18 (6.0) 13 (4.3) 31 (5.2) Mixed glioma 2 (0.7) 2 (0.7) 4 (0.7) 18 (6.0) 9 (3.0) 27 (4.5) Total 42 (14.0) 35 (12.0) 77 (12.8) 148 (49.3) 131 (43.7) 279 (46.5) a: Number of rats examined. b: Percentage. Brain lesions were induced with intravenous injection of ENU 10 mg/kg in F344 rats on day 20 of gestation.

Astrocytoma GFAP PCNA Vimentin

Atypical hyperplasia of astroglia GFAP PCNA

Oligodendroglioma PCNA Vimentin

Atypical hyperplasia of oligodendroglia PCNA

Medulloblastoma Silver impregnation PCNA

Meningioma AZAN PCNA

Granular cell tumor PAS PCNA

Malignant reticulosis ED1 PAS PCNA

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