●Classification of spontaneous brain tumors in rats
1. Tumors of Neuroepithelial TissueA. Astrocytic and oligodendroglial tumors
AstrocytomaOligodendrogliomaMixed glioma (oligo-astrocytoma)Anaplastic glioma
B. Ependymal and choroid plexus tumorsEpendymomaChoroid plexus papillomaChoroid plexus carcinoma
C. Pineal gland neoplasmsPinealomaPineal gland carcinoma
D. Neuronal and primitive bipotential precursorcell neoplasmsGangliogliomaGanglioneuromaMedulloblastoma
2. Tumors of Nerve Sheath CellsSchwannoma (benign or malignant)
3. Tumors of Meninges and Related TissuesMeningiomaMeningeal sarcomaGranular cell tumorMalignant melanoma
4. Primary LymphomasMalignant reticulosis
Central Nervous System Neoplasms in the Rat (Solleveld HA, et al., 1991)
●Incidence of spontaneous brain tumors in NIBS
Incidence of Spontaneous Brain Tumors in F344 Rats in NIBSa
Tumors Male Female Totaln=2142b 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 FacilitiesTumor Type NIBSa NCIb NTPc NIEHSd NIHSe IETf BRCg
n=2142h n=1794 n=1928 n=1335 n=296 n=960 n=696Neuroglia 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 FacilitiesTumor Type NIBSa NCIb NTPc NIEHSd NIHSe IETf BRCg
n=2092h n=1754 n=1969 n=1349 n=297 n=959 n=700Neuroglia 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.
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
NIBS NCI NTP NIEHS NIHS IET BRC
MaleFemale
Incidences of Spontaneous Brain Tumors in F344 Rats in Seven Facilities
Inci
denc
e (%
)
●Summary of Spontaneous Brain Tumors in F344 Rats
●Incidence : Very low
●Sex ratio : Male > Female
●Tumor type : 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 Totaln=300a 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
PCNA Vimentin
Oligodendroglioma
Atypical hyperplasia of oligodendroglia
PCNA
Medulloblastoma
Silver impregnation PCNA
Meningioma
AZAN PCNA
Granular cell tumor
PAS PCNA
Malignant reticulosis
ED1 PAS PCNA
