TABLE 3.
Rare Neoplastic Alterations Observed in the Long-Term Animal Study
| Treatment group | Number of mice with histopathological alterations/effective number of mice in treatment group and comparison with Control group by Fisher’s exact test
|
||||
|---|---|---|---|---|---|
| Benign lesions
|
Malignant lesions
|
Totalb | |||
| Histopathology | Fraction | Histopathology | Fraction | ||
| 1. Control | Lipoma with calcification | 2/52 = 0.04 | Hemangiosarcoma | 2/52 = 0.04 | 4/52 = 0.08 |
| Lung—multiple bronchioloalveolar adenomas | Sternal muscle—leiomyosarcoma | ||||
| 2. Antioxidants | Liver—hepatoblastoma | 2/53 = 0.04 (P = 1) | Spleen—malignant fibrous histiocytoma and histiocytic sarcoma | 1/53 = 0.02 (P > 0.6, one mouse had 2 lesions) | 3/53 = 0.06 (P > 0.7) |
| Pancreas—islet cell adenoma | |||||
| 3. BBIC | Liver—hepatoblastoma | 2/53 = 0.04 (P = 1) | Lung—papillary bronchioloalveolar adenocarcinoma | 1/53 = 0.02 (P > 0.6) | 3/53 = 0.06 (P > 0.7) |
| Liver—cholangioma | |||||
| 4. Protons | Lung—bronchioloalveolar adenoma, two mice | 5/45 = 0.11 (P > 0.2) | Kidney—metastatic pericapsular adenocarcinoma | 6/45 = 0.13b (P > 0.1) | 11/45 = 0.24 (P < 0.03) |
| Liver—cholangioma | Liver—cholangiocarcinoma | ||||
| Adrenal gland—pheochromocytoma | Harderian gland tumors—adenocarcinoma—4 micec | ||||
| Kidney—renal tubular adenoma (unilateral) | |||||
| 5. Protons and antioxidants | None | 0/48 = 0.00 (P > 0.4) | Sternal muscle—fibrosarcoma | 1/48 = 0.02 (P = 1) | 1/48 = 0.02 (P > 0.3) |
| 6. Protons and BBIC | None | 0/41 = 0.00 (P > 0.5) | Fibrosarcoma | 1/41 = 0.02 (P = 1) | 1/41 = 0.02 (P > 0.3) |
| 7. Iron ions | Gross lesion—lipoma | 4/64 = 0.06 (P > 0.6) | Liver—hemangiosarcoma | 5/64 = 0.08 (P > 0.4) | 9/64 = 0.14 (P > 0.3) |
| Lung—solid bronchioloalveolar adenoma | Sternal muscle—rhabdomyosarcoma | ||||
| Harderian gland tumors-adenomas—2 micec | Harderian gland tumors—adenocarcinomas—3 micec | ||||
| 8. Iron ions and antioxidants | Hemangioma (subcutis) | 1/47 = 0.02 (P = 1) | Kidney—renal tubular cell carcinoma | 3/47 = 0.06d (P > 0.6) | 3/47 = 0.06d (P = 1) |
| Small intestine—adenocarcinoma with desmoplasia | |||||
| Metastatic adenocarcinoma with abscess | |||||
| 9. Iron ions and BBIC | None | 0/66 = 0.00 (P > 0.1) | Kidney—pericapsular rhabdomyosarcoma | 3/66 = 0.05 (P = 1) | 3/66 = 0.05 (P > 0.6) |
| Kidney—renal tubule carcinoma | |||||
| Fibrosarcoma | |||||
The results for the fractions of animals (with Total—Benign and Malignant lesions) for the various treatment groups were merged as follows for further statistical analyses: (1) spontaneous lymphoma development = Groups 1 (4/52) + 2 (3/53) + 3 (3/53) = 10/158, (2) space radiation exposure—protons and iron ions = Groups 4 (11/45) + 7 (9/64) = 20/109, (3) space radiation exposure with countermeasures (antioxidants or BBIC) = Groups 5 (1/48) + 6 (1/41) + 8 (3/47) + 9 (3/66) = 8/202. The statistical analyses for these merged treatment groups gave the following results: Merged Groups (1) compared to (2), P = 0.004, Merged Groups (1) compared to (3), P = 0.4, and Merged Groups (2) compared to (3), P = 0.0001.
Two metastatic lesions were counted in two mice with malignant lesions (one in Group 4 and one in Group 8). Although it is clear that there was an adenocarcinoma in each of these animals, the primary sites were not identified.
The results for the fractions of animals with Harderian adenoma or adenocarcinoma for the various treatment groups were merged as follows for further statistical analyses: (1) spontaneous harderian adenoma or adenocarcinoma development = Groups 1 (0/52) + 2 (0/53) + 3 (0/53) = 0/158, (2) space radiation exposure—protons and iron ions = Groups 4 (4/45) + 7 (5/64) = 9/109, (3) space radiation exposure with countermeasures (antioxidants or BBIC) = Groups 5 (0/48) + 6 (0/41) + 8 (0/47) + 9 (0/66) = 0/202. The statistical analyses for these merged treatment groups gave the following results: Merged Groups (1) compared to (2), P = 0.0003; Merged Groups (2) compared to (3), P = 0.0001.
One animal had both a benign and a malignant tumor in this treatment group.