CELL KINETICS STUDY OF A MOUSE SUBCUTANEOUS SARCOMA INDUCED BY 4NQO WITH THE BROMODEOXYURIDINE/IODODEOXYURIDINE DOUBLE LABELING METHOD

Abstract

We studied cell kinetics of a mouse sarcoma induced by a subcutaneous injection of 4-nitroquioline 1-oxide by an immunohistochemical method. A mouse bearing a sarcoma received intraperitoneal injections of two thymidine analogues, iododeoxyuridine (IdUrd) and bromodeoxyuridine (BrdUrd) 3 hr and 1 hr, respectively, before sacrifice, and BrdUrd/IdUrd double immunostaining using anti-BrdUrd monospecific antibody and anti-BrdUrd/IdUrd bi-specific antibody was performed to evaluate BrdUrd labeling index (LI), S-phase duration (ts), cell cycle time (Tc), and turn-over time (To) in the tumor cells and to characterize changes of these parameters in the different histological tumor patterns. Histologically, the sarcoma was composed of spindle cells and giant cells, and resembled malignant fibrous histiocytoma. The spindle cells formed two different histological patterns; fascicular and hemangiopericytomatous patterns. In the spindle tumor cells in the fascicular region, LI was 21.8%, is was 7.2 hr, Tc was 26.5 hr, and To was 3.1 hr. In the spindle cells in the hemangiopericytomatous region, LI was 14.2%, ts was 9.5 hr, Tc was 46.8 hr, and To was 66.8 hr. In the giant tumor cells, LI was 38.7%, ts was 24 hr, Tc was 25.4 hr, To was 31.7 hr. Thus, in this study, we revealed that the cell kinetics parameters were dependent on the histological tumor pattern and the tumor cell type in a sarcoma with heterogeneous histological components. The BrdUrd/IdUrd double immunostaining method is an easy and reliable method, and is useful to gain various cell kinetics parameters of animal tumors