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Reduced hematopoietic function and enhanced radiosensitivity of transforming growth factor‐β1 transgenic mice
Author(s) -
Vodovotz Yoram,
Lucia M. Scott,
DeLucca AnneMarie,
Mitchell James B.,
Kopp Jeffrey B.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000220)90:1<13::aid-ijc2>3.0.co;2-u
Subject(s) - radiosensitivity , haematopoiesis , transgene , transforming growth factor , biology , genetically modified mouse , function (biology) , cancer research , radiation tolerance , growth factor , microbiology and biotechnology , immunology , medicine , genetics , stem cell , gene , radiation therapy , receptor
The cytokine transforming growth factor‐β1 (TGF‐β1) has been implicated in some tissue responses to radiation. Previous studies have demonstrated that exogenous TGF‐β1 increased the lethality of radiation in mice, but the effects of endogenous TGF‐β1 have not been investigated. To this end, we examined mice that are transgenic for active TGF‐β1 (Alb/TGF‐β1), over‐expressed via an albumin promoter in the liver with resultant elevation of circulating levels of this cytokine. Alb/TGF‐β1 mice subjected to 8 Gy of total body irradiation at 3 or 5 weeks of age experienced significantly higher mortality than wild type age‐ and sex‐matched controls by 1 to 2 weeks after irradiation. Alb/TGF‐β1 3 weeks of age also succumbed to 2 and 4 Gy of whole‐body irradiation, while no mortality was observed in wild type mice. Four‐week‐old Alb/TGF‐β1 mice exhibited mild anemia and mild uremia. At one week after whole body irradiation with 2 Gy, 4‐week‐old Alb/TGF‐β1 mice had significantly reduced white blood cell counts, hematocrit, and platelet counts. Histopathologically, irradiated Alb/TGF‐β1 mice exhibited decreased bone marrow cellularity and decreased splenic extramedullary hematopoiesis. These results suggest that chronic over‐expression of active TGF‐β1 is associated with increased radiosensitivity and that this effect may be mediated by increased sensitivity of bone marrow to the suppressive effects of radiation. Since TGF‐β1 levels can be greatly elevated in patients with certain tumors, these findings may be significant for radiotherapy. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 13–21 (2000) . Published 2000 Wiley‐Liss, Inc.