EFFECT OF IN-VIVO ADMINISTRATION OF ALL-TRANS-RETINOIC ACID ON THE HEMATOPOIETIC-CELL POPULATIONS OF THE SPLEEN AND BONE-MARROW - PROFOUND STRAIN DIFFERENCES BETWEEN A J AND C57BL/6J MICE/

All trans-retinoic acid (ATRA) is currently the subject of much intere st as a possible anti-tumor therapeutic agent, especially for leukemia s. One postulated mechanism for its ameliorative action on tumor growt h is via stimulating cells of the immune system and its accessory cell s, Mice of the A/J strain have an unusually high frequency of leukemia , whereas C57BL/6J mice rarely develop leukemia, and moreover, unlike AIS mice, have strong resistance to a variety of pathogens, The purpos e of the study reported here was twofold: to investigate whether A/J m ice have quantitative deficiencies in their specific and nonspecific d isease defense mechanisms (lymphoid, granuloid, and monocytoid cells) relative to those of C57BL/6J mice, and if so, whether in vivo adminis tration of an ATRA could quantitatively augment these cells in the maj or organs housing them: the spleen and the bone marrow. Furthermore, f or the lymphoid and granuloid lineages, absolute numbers of precursors and of differentiated (mature) cells also were enumerated, The result s indicate that A/J mice have significantly lower numbers of lymphoid, granuloid, and monocytoid-but not erythroid-cells in the spleen and/o r bone marrow than do C57BL/6J mice. Also, sensitivity to ATRA was gen erally more profound in A/J mice than in C57BL/6 mice with respect to several hemopoietic cell lineages, These observations collectively sug gest a need for considerable prudence ins selection of inbred strains of mice, not only because of the possibility of wide in interstrain va riations in hemopoietic and immune cell-mediated functions, hut also b ecause of potential differences in the responses of various strains of common laboratory mice to pharmacalogic agents.