Distribution and Lysis of Weakly and Strongly Immunogenic Malignant Lymphoid Cells in Normal and Immune Mice: Effects of Prior Exposure to Heat or X-Irradiation2

Abstract

With the use of cells doubly labeled with 51Cr and 125I, an analysis was made of the distribution and lysis in normal and immune syngeneic C58 mice of weakly immunogenic malignant lymphocytes (Ib) and a highly immunogenic variant (IbN) derived from them. The results showed that 51Cr release was not a valid measure of tumor cell lysis in vivo. Prior exposure to 55 degrees C for 30 minutes caused Ib to lyse immediately after iv injection. Prior X-irradiation (10,000 R) enhanced the lysis of Ib in vivo but had only minor effects on IbN. In normal mice 125I-labeled Ib were entrapped in the lungs (approximately to 95%) immediately after iv injection, released in a diphasic manner, and then accumulated in the liver, spleen, bone marrow, and lymph nodes. In immune mice initial entrapment of Ib in the lungs was only about 42%, and label did not accumulate in the described organs. Heat-inactivated Ib were not retained to a significant degree in any of the organs of normal or immune mice. IbN were retained initially (2 hr) at values lower than Ib in the whole body, lungs, and livers of normal mice. 125I-labeled Ib were used to analyze how they were distributed and lysed in normal and immune mice during the first 6 hours after iv injection. To account for the loss of 125I from a tissue because of cell lysis (as distinct from cell redistribution), the amount of 125I associated with cells and blood plasma, and lost from the whole body, was quantified. A significant loss of 125I from the whole body began at 2 hours and continued at a linear rate thereafter. Non-cell-associated 125I occurred in the blood plasma at 1-2 hours and increased at a linear rate thereafter. These results made it possible to distinguish between loss of 125I from a tissue because of cell lysis as distinct from the redistribution of intact labeled cells.