Effect of in vivo administration of all trans-retinoic acid on the hemopoietic cell populations of the spleen and bone marrow: profound strain differences between A/J and C57BL/6J mice

Abstract

All trans-retinoic acid (ATRA) is currently the subject of much interest as a possible anti-tumor therapeutic agent, especially for leukemias. One postulated mechanism for its ameliorative action on tumor growth is via stimulating cells of the immune system and its accessory cells. Mice of the A/J strain have an unusually high frequency of leukemia, whereas C57BL/6J mice rarely develop leukemia, and moreover, unlike A/J mice, have strong resistance to a variety of pathogens. The purpose of the study reported here was twofold: to investigate whether A/J mice have quantitative deficiencies in their specific and nonspecific disease defense mechanisms (lymphoid, granuloid, and monocytoid cells) relative to those of C57BL/6J mice, and if so, whether in vivo administration of an ATRA could quantitatively augment these cells in the major organs housing them: the spleen and the bone marrow. Furthermore, for the lymphoid and granuloid lineages, absolute numbers of precursors and of differentiated (mature) cells also were enumerated. The results indicate that A/J mice have significantly lower numbers of lymphoid, granuloid, and monocytoid--but not erythroid--cells in the spleen and/or bone marrow than do C57BL/6J mice. Also, sensitivity to ATRA was generally more profound in A/J mice than in C57BL/6 mice with respect to several hemopoietic cell lineages. These observations collectively suggest a need for considerable prudence in selection of inbred strains of mice, not only because of the possibility of wide interstrain variations in hemopoietic and immune cell-mediated functions, but also because of potential differences in the responses of various strains of common laboratory mice to pharmacologic agents.