NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TRANSGENIC MODEL EVALUATION II (GLYCIDOL) DATE: 03/31/04 EXPERIMENT: 99035 TEST: 01 TIME: 12:56:50 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: C99035 PATHOLOGIST: MISSING CAS: 556-52-5 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #1 REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TRANSGENIC MODEL EVALUATION II (GLYCIDOL) DATE: 03/31/04 EXPERIMENT: 99035 TEST: 01 TIME: 12:56:50 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: C99035 PATHOLOGIST: MISSING CAS: 556-52-5 Mice(P16(INK4A)/(+/-) (C57BL/6)) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED. --------------- Bone Marrow Brain Lung Spleen NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus TRANSGENIC MODEL EVALUATION II (GLYCIDOL) DATE: 03/31/04 EXPERIMENT: 99035 TEST: 01 TIME: 12:56:50 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: C99035 PATHOLOGIST: MISSING CAS: 556-52-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TRANSGENIC MODEL EVALUATION II (GLY =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma All Organs Histiocytic Sarcoma Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma Stomach, Forestomach Squamous Cell Papilloma All Organs Histiocytic Sarcoma Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 1 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 2/15 (13%) 7/15 (47%) 3/15 (20%) | |POLY-3 RATE (b) | 1/13.95 0/14.74 2/13.80 7/14.37 3/11.42 | |POLY-3 PERCENT (g) | 7.2% 0.0% 14.5% 48.7% 26.3% | |TERMINAL (d) | 1/13 (8%) 0/14 (0%) 2/13 (15%) 7/14 (50%) 3/7 (43%) | |FIRST INCIDENCE | 280 (T) --- 280 (T) 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.485N P=0.500 P=0.026 * P=0.104 | |POLY 3 | P=0.009 ** P=0.489N P=0.496 P=0.013 * P=0.223 | |POLY 1.5 | P=0.019 * P=0.493N P=0.496 P=0.013 * P=0.255 | |POLY 6 | P=0.004 ** P=0.485N P=0.499 P=0.014 * P=0.186 | |LOGISTIC REGRESSION| P=0.003 ** (e) P=0.500 P=0.026 * P=0.104 | |COCH-ARM / FISHERS | P=0.053 P=0.500N P=0.500 P=0.018 * P=0.299 | |ORDER RESTRICTED | P=0.014 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 0/15 (0%) 1/15 (7%) 4/15 (27%) | |POLY-3 RATE (b) | 0/13.88 1/14.62 0/14.15 1/14.62 4/13.34 | |POLY-3 PERCENT (g) | 0.0% 6.8% 0.0% 6.8% 30.0% | |TERMINAL (d) | 0/13 (0%) 1/14 (7%) 0/12 (0%) 1/14 (7%) 2/9 (22%) | |FIRST INCIDENCE | --- 281 (T) --- 281 (T) 208 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P=0.515 (e) P=0.515 P=0.038 * | |POLY 3 | P=0.003 ** P=0.510 (e) P=0.510 P=0.039 * | |POLY 1.5 | P=0.004 ** P=0.510 (e) P=0.510 P=0.042 * | |POLY 6 | P=0.003 ** P=0.509 (e) P=0.509 P=0.037 * | |LOGISTIC REGRESSION| P=0.007 ** P=0.515 (e) P=0.515 P=0.056 | |COCH-ARM / FISHERS | P=0.005 ** P=0.500 (e) P=0.500 P=0.050 | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 2 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 1/15 (7%) 1/15 (7%) 3/15 (20%) 0/15 (0%) | |POLY-3 RATE (b) | 2/13.95 1/14.74 1/13.80 3/14.37 0/11.42 | |POLY-3 PERCENT (g) | 14.3% 6.8% 7.2% 20.9% 0.0% | |TERMINAL (d) | 2/13 (15%) 1/14 (7%) 1/13 (8%) 3/14 (21%) 0/7 (0%) | |FIRST INCIDENCE | 280 (T) 280 (T) 280 (T) 280 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.471N P=0.473N P=0.500N P=0.536 P=0.380N | |POLY 3 | P=0.385N P=0.480N P=0.504N P=0.514 P=0.279N | |POLY 1.5 | P=0.342N P=0.488N P=0.504N P=0.508 P=0.257N | |POLY 6 | P=0.439N P=0.473N P=0.501N P=0.523 P=0.310N | |LOGISTIC REGRESSION| P=0.471N P=0.473N P=0.500N P=0.536 (e) | |COCH-ARM / FISHERS | P=0.287N P=0.500N P=0.500N P=0.500 P=0.241N | |ORDER RESTRICTED | P=0.220N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 1/14.62 0/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.8% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 1/14 (7%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- 281 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.603 (e) (e) P=0.515 (e) | |POLY 3 | P=0.560 (e) (e) P=0.510 (e) | |POLY 1.5 | P=0.591 (e) (e) P=0.510 (e) | |POLY 6 | P=0.529 (e) (e) P=0.509 (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.515 (e) | |COCH-ARM / FISHERS | P=0.639 (e) (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.388 (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 3 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 3/15 (20%) 1/15 (7%) 3/15 (20%) 8/15 (53%) 3/15 (20%) | |POLY-3 RATE (b) | 3/13.95 1/14.74 3/13.80 8/14.37 3/11.42 | |POLY-3 PERCENT (g) | 21.5% 6.8% 21.7% 55.7% 26.3% | |TERMINAL (d) | 3/13 (23%) 1/14 (7%) 3/13 (23%) 8/14 (57%) 3/7 (43%) | |FIRST INCIDENCE | 280 (T) 280 (T) 280 (T) 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032 * P=0.271N P=0.676 P=0.084 P=0.345 | |POLY 3 | P=0.093 P=0.277N P=0.668 P=0.063 P=0.573 | |POLY 1.5 | P=0.146 P=0.285N P=0.666 P=0.061 P=0.618 | |POLY 6 | P=0.048 * P=0.269N P=0.672 P=0.067 P=0.509 | |LOGISTIC REGRESSION| P=0.032 * P=0.271N P=0.676 P=0.084 P=0.345 | |COCH-ARM / FISHERS | P=0.252 P=0.299N P=0.674N P=0.064 P=0.674N | |ORDER RESTRICTED | P=0.078 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 0/15 (0%) 2/15 (13%) 4/15 (27%) | |POLY-3 RATE (b) | 0/13.88 1/14.62 0/14.15 2/14.62 4/13.34 | |POLY-3 PERCENT (g) | 0.0% 6.8% 0.0% 13.7% 30.0% | |TERMINAL (d) | 0/13 (0%) 1/14 (7%) 0/12 (0%) 2/14 (14%) 2/9 (22%) | |FIRST INCIDENCE | --- 281 (T) --- 281 (T) 208 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** P=0.515 (e) P=0.252 P=0.038 * | |POLY 3 | P=0.004 ** P=0.510 (e) P=0.243 P=0.039 * | |POLY 1.5 | P=0.004 ** P=0.510 (e) P=0.243 P=0.042 * | |POLY 6 | P=0.004 ** P=0.509 (e) P=0.242 P=0.037 * | |LOGISTIC REGRESSION| P=0.007 ** P=0.515 (e) P=0.252 P=0.056 | |COCH-ARM / FISHERS | P=0.006 ** P=0.500 (e) P=0.241 P=0.050 | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 4 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 1/11.95 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 8.4% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 218 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.112 (e) (e) (e) P=0.452 | |POLY 3 | P=0.127 (e) (e) (e) P=0.469 | |POLY 1.5 | P=0.134 (e) (e) (e) P=0.482 | |POLY 6 | P=0.119 (e) (e) (e) P=0.452 | |LOGISTIC REGRESSION| P=0.229 (e) (e) (e) P=0.684 | |COCH-ARM / FISHERS | P=0.143 (e) (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.065 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 1/14.62 3/12.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.8% 24.1% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 1/14 (7%) 1/9 (11%) | |FIRST INCIDENCE | --- --- --- 281 (T) 278 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** (e) (e) P=0.515 P=0.081 | |POLY 3 | P=0.003 ** (e) (e) P=0.510 P=0.085 | |POLY 1.5 | P=0.004 ** (e) (e) P=0.510 P=0.094 | |POLY 6 | P=0.003 ** (e) (e) P=0.509 P=0.077 | |LOGISTIC REGRESSION| P=0.002 ** (e) (e) P=0.515 P=0.079 | |COCH-ARM / FISHERS | P=0.005 ** (e) (e) P=0.500 P=0.112 | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 5 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 2/15 (13%) 6/15 (40%) 9/15 (60%) 5/15 (33%) 11/15 (73%) | |POLY-3 RATE (b) | 2/14.61 6/15.00 9/15.00 5/14.37 11/14.47 | |POLY-3 PERCENT (g) | 13.7% 40.0% 60.0% 34.8% 76.0% | |TERMINAL (d) | 1/13 (8%) 5/14 (36%) 7/13 (54%) 5/14 (36%) 4/7 (57%) | |FIRST INCIDENCE | 196 253 146 280 (T) 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.150 P=0.021 * P=0.231 P<0.001 ** | |POLY 3 | P=0.002 ** P=0.113 P=0.007 ** P=0.186 P<0.001 ** | |POLY 1.5 | P=0.003 ** P=0.109 P=0.007 ** P=0.189 P<0.001 ** | |POLY 6 | P=0.002 ** P=0.118 P=0.008 ** P=0.186 P<0.001 ** | |LOGISTIC REGRESSION| P=0.023 * P=0.047 * P=0.008 ** P=0.177 P=0.007 ** | |COCH-ARM / FISHERS | P=0.005 ** P=0.107 P=0.010 * P=0.195 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 9/15 (60%) 9/15 (60%) 12/15 (80%) 10/15 (67%) 13/15 (87%) | |POLY-3 RATE (b) | 9/14.03 9/15.00 12/15.00 10/15.00 13/14.97 | |POLY-3 PERCENT (g) | 64.2% 60.0% 80.0% 66.7% 86.9% | |TERMINAL (d) | 8/13 (62%) 8/14 (57%) 9/12 (75%) 9/14 (64%) 8/9 (89%) | |FIRST INCIDENCE | 267 239 232 239 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** P=0.550N P=0.194 P=0.590 P=0.026 * | |POLY 3 | P=0.102 P=0.558N P=0.299 P=0.595 P=0.160 | |POLY 1.5 | P=0.099 P=0.571N P=0.285 P=0.582 P=0.150 | |POLY 6 | P=0.101 P=0.556N P=0.302 P=0.598 P=0.159 | |LOGISTIC REGRESSION| P=0.076 P=0.590N P=0.245 P=0.568 P=0.099 | |COCH-ARM / FISHERS | P=0.076 P=0.645N P=0.213 P=0.500 P=0.107 | |ORDER RESTRICTED | P=0.115 (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 6 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) | |POLY-3 RATE (b) | 2/13.95 0/14.74 0/13.80 1/15.00 0/11.42 | |POLY-3 PERCENT (g) | 14.3% 0.0% 0.0% 6.7% 0.0% | |TERMINAL (d) | 2/13 (15%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | 280 (T) --- --- 201 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.327N P=0.219N P=0.235N P=0.475N P=0.380N | |POLY 3 | P=0.287N P=0.218N P=0.233N P=0.474N P=0.279N | |POLY 1.5 | P=0.279N P=0.223N P=0.234N P=0.485N P=0.257N | |POLY 6 | P=0.292N P=0.214N P=0.231N P=0.462N P=0.310N | |LOGISTIC REGRESSION| P=0.201N (e) (e) P=0.543N (e) | |COCH-ARM / FISHERS | P=0.266N P=0.241N P=0.241N P=0.500N P=0.241N | |ORDER RESTRICTED | P=0.070N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 0/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 7 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 1/15 (7%) 2/15 (13%) 2/15 (13%) 7/15 (47%) 4/15 (27%) | |POLY-3 RATE (b) | 1/13.95 2/14.74 2/13.80 7/14.37 4/11.95 | |POLY-3 PERCENT (g) | 7.2% 13.6% 14.5% 48.7% 33.5% | |TERMINAL (d) | 1/13 (8%) 2/14 (14%) 2/13 (15%) 7/14 (50%) 3/7 (43%) | |FIRST INCIDENCE | 280 (T) 280 (T) 280 (T) 280 (T) 218 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.527 P=0.500 P=0.026 * P=0.050 | |POLY 3 | P=0.018 * P=0.519 P=0.496 P=0.013 * P=0.112 | |POLY 1.5 | P=0.028 * P=0.512 P=0.496 P=0.013 * P=0.132 | |POLY 6 | P=0.010 * P=0.527 P=0.499 P=0.014 * P=0.090 | |LOGISTIC REGRESSION| P=0.015 * P=0.527 P=0.500 P=0.026 * P=0.113 | |COCH-ARM / FISHERS | P=0.055 P=0.500 P=0.500 P=0.018 * P=0.165 | |ORDER RESTRICTED | P=0.025 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 0/15 (0%) 2/15 (13%) 7/15 (47%) | |POLY-3 RATE (b) | 0/13.88 1/14.62 0/14.15 2/14.62 7/13.40 | |POLY-3 PERCENT (g) | 0.0% 6.8% 0.0% 13.7% 52.3% | |TERMINAL (d) | 0/13 (0%) 1/14 (7%) 0/12 (0%) 2/14 (14%) 3/9 (33%) | |FIRST INCIDENCE | --- 281 (T) --- 281 (T) 208 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.515 (e) P=0.252 P=0.004 ** | |POLY 3 | P<0.001 ** P=0.510 (e) P=0.243 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.510 (e) P=0.243 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.509 (e) P=0.242 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.515 (e) P=0.252 P=0.004 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 (e) P=0.241 P=0.003 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 8 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 6/15 (40%) 7/15 (47%) 10/15 (67%) 9/15 (60%) 11/15 (73%) | |POLY-3 RATE (b) | 6/15.00 7/15.00 10/15.00 9/15.00 11/14.47 | |POLY-3 PERCENT (g) | 40.0% 46.7% 66.7% 60.0% 76.0% | |TERMINAL (d) | 4/13 (31%) 6/14 (43%) 8/13 (62%) 8/14 (57%) 4/7 (57%) | |FIRST INCIDENCE | 196 253 146 201 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.561 P=0.180 P=0.315 P=0.023 * | |POLY 3 | P=0.036 * P=0.500 P=0.136 P=0.236 P=0.047 * | |POLY 1.5 | P=0.041 * P=0.500 P=0.136 P=0.236 P=0.054 | |POLY 6 | P=0.031 * P=0.500 P=0.136 P=0.236 P=0.040 * | |LOGISTIC REGRESSION| P=0.181 (e) (e) (e) P=0.207 | |COCH-ARM / FISHERS | P=0.049 * P=0.500 P=0.136 P=0.233 P=0.070 | |ORDER RESTRICTED | P=0.033 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 10/15 (67%) 9/15 (60%) 12/15 (80%) 11/15 (73%) 14/15 (93%) | |POLY-3 RATE (b) | 10/15.00 9/15.00 12/15.00 11/15.00 14/15.00 | |POLY-3 PERCENT (g) | 66.7% 60.0% 80.0% 73.3% 93.3% | |TERMINAL (d) | 8/13 (62%) 8/14 (57%) 9/12 (75%) 10/14 (71%) 8/9 (89%) | |FIRST INCIDENCE | 83 239 232 239 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.006 ** P=0.420N P=0.303 P=0.591 P=0.036 * | |POLY 3 | P=0.037 * P=0.500N P=0.343 P=0.500 P=0.080 | |POLY 1.5 | P=0.037 * P=0.500N P=0.343 P=0.500 P=0.080 | |POLY 6 | P=0.037 * P=0.500N P=0.343 P=0.500 P=0.080 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.037 * P=0.500N P=0.341 P=0.500 P=0.084 | |ORDER RESTRICTED | P=0.042 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 03/31/04 EXPERIMENT: 99035 TEST: 01 Page 9 Statistical Analysis of Primary Tumors in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 7/15 (47%) 8/15 (53%) 12/15 (80%) 12/15 (80%) 12/15 (80%) | |POLY-3 RATE (b) | 7/15.00 8/15.00 12/15.00 12/15.00 12/14.47 | |POLY-3 PERCENT (g) | 46.7% 53.3% 80.0% 80.0% 83.0% | |TERMINAL (d) | 5/13 (39%) 7/14 (50%) 10/13 (77%) 11/14 (79%) 5/7 (71%) | |FIRST INCIDENCE | 196 253 146 201 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.569 P=0.110 P=0.140 P=0.016 * | |POLY 3 | P=0.018 * P=0.500 P=0.059 P=0.059 P=0.039 * | |POLY 1.5 | P=0.023 * P=0.500 P=0.059 P=0.059 P=0.047 * | |POLY 6 | P=0.014 * P=0.500 P=0.059 P=0.059 P=0.032 * | |LOGISTIC REGRESSION| P=0.086 (e) (e) (e) P=0.160 | |COCH-ARM / FISHERS | P=0.033 * P=0.500 P=0.064 P=0.064 P=0.064 | |ORDER RESTRICTED | P=0.021 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # # | |----------- | | |OVERALL (a) | 10/15 (67%) 9/15 (60%) 12/15 (80%) 12/15 (80%) 14/15 (93%) | |POLY-3 RATE (b) | 10/15.00 9/15.00 12/15.00 12/15.00 14/15.00 | |POLY-3 PERCENT (g) | 66.7% 60.0% 80.0% 80.0% 93.3% | |TERMINAL (d) | 8/13 (62%) 8/14 (57%) 9/12 (75%) 11/14 (79%) 8/9 (89%) | |FIRST INCIDENCE | 83 239 232 239 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004 ** P=0.420N P=0.303 P=0.465 P=0.036 * | |POLY 3 | P=0.027 * P=0.500N P=0.343 P=0.343 P=0.080 | |POLY 1.5 | P=0.027 * P=0.500N P=0.343 P=0.343 P=0.080 | |POLY 6 | P=0.027 * P=0.500N P=0.343 P=0.343 P=0.080 | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.028 * P=0.500N P=0.341 P=0.341 P=0.084 | |ORDER RESTRICTED | P=0.038 * (e) (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).