strontium-radioisotopes and Hyperplasia

We previously described a preleukemic state induced by Moloney murine leukemia virus (Mo-MuLV) characterized by hematopoietic hyperplasia in the spleen. Further experiments suggested that splenic hyperplasia results from inhibitory effects in the bone marrow, leading to compensatory extramedullary hematopoiesis. An enhancer variant of Mo-MuLV, Mo + PyF101 Mo-MuLV, fails to induce preleukemic hyperplasia and has greatly reduced leukemogenicity, indicating the importance of this state to efficient leukemogenesis. An alternative method for induction of preleukemic hyperplasia was sought. Treatment of mice with 89Sr causes specific ablation of bone marrow hematopoiesis and compensatory extramedullary hematopoiesis in spleen and nodes. NIH Swiss mice were inoculated neonatally with Mo + PyF101 Mo-MuLV and treated with 89Sr at 6 weeks of age. Approximately 85% developed lymphoid leukemia with a time course resembling that caused by wild-type Mo-MuLV. In contrast, very few animals treated with Mo + PyF101 Mo-MuLV or 89Sr alone developed disease. In approximately one-third of cases, the Mo + PyF101 Mo-MuLV proviruses were found at common sites for wild-type Mo-MuLV-induced tumors (c-myc, pvt-1, and pim-1), indicating that this virus is capable of performing insertional activation in T-lymphoid cells. These results support the proposal that splenic hyperplasia results from inhibitory effects in the bone marrow. They also indicate that Mo + PyF101 Mo-MuLV is blocked in early and not late events in leukemogenesis.

Topics: Animals; Animals, Newborn; Blotting, Southern; Bone Marrow; DNA, Neoplasm; DNA, Viral; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Hematopoiesis, Extramedullary; Hyperplasia; Mice; Moloney murine leukemia virus; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Preleukemia; Proto-Oncogenes; Proviruses; Repetitive Sequences, Nucleic Acid; Spleen; Strontium Radioisotopes

The present investigation was initiated to analyse the carcinogenic effect of combined treatment with 90Sr and oestrogenic hormones or corticosteroids in inbred CBA mice. Pituitary tumours appeared in a remarkably high incidence in mice treated with oestrogens + 90Sr in low doses--0.925 kBq/g body weight (44%) and 1.850 kBq/g body weight (37%)--as compared with mice treated with 90Sr only--1 and 3 per cent, respectively. The syncancerogenic effect is ascribed the oestrogen induced proliferation of pituitary cells and their increased sensitivity to radiation. The reverse relation found between number of pituitary tumours and dose of 90Sr in oestrogen treated mice is explained by the reduction of the survival time with increasing dose. Preneoplastic histologic changes of the pituitary are described and pituitary tumours which mainly appeared in pars distalis, are classified according to the growth and tinctorial characteristics.

Topics: Adenoma, Acidophil; Adenoma, Chromophobe; Animals; Estradiol; Estrogens; Hyperplasia; Male; Methylprednisolone; Mice; Mice, Inbred CBA; Neoplasms, Experimental; Organophosphorus Compounds; Pituitary Gland; Pituitary Neoplasms; Strontium Radioisotopes

Topics: Animals; Cat Diseases; Cats; Hyperplasia; Inclusion Bodies; Mast Cells; Mast-Cell Sarcoma; Microscopy, Electron; Mitochondria; Radiation Effects; Strontium Radioisotopes