The accumulation of p53 protein following whole body irradiation of adult mice was studied using a new polyclonal antibody to mouse p53. While dramatic accumulation of the protein was apparent in splenocytes, thymocytes and osteocytes no p53 protein accumulation was detected in the hepatocytes of the irradiated mouse. Thus, the upstream initiating signals that control the induction of p53 are controlled in a tissue specific manner. While massive apoptosis accompanies p53 induction in thymocytes and splenocytes it is not seen in the osteocytes. Thus the downstream consequences of p53 induction are also tightly controlled. These results have profound significance for an understanding of the role of the p53 tumour suppression pathway in different tissues.

No abstract

During the first 4 days after the intravenous administration of a lethal dose (100 μg) of mustine hydrochloride to mice, there is a marked decrease in the weights of the lymph nodes, thymus and spleen and in the cellularity of the femoral bone marrow. In the subsequent 4 days, the cellularity of the bone marrow increases to values within the normal range while the weights of the lymph nodes, thymus and spleen remain exceedingly small. In this bone marrow regenerating after the injection of mustine hydrochloride, 94% of the recognisable haematopoietic cells are granulocytes at various stages of maturation.

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 μg (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration from days 5–12. The thymus, lymph nodes, and spleen commenced regeneration during the second week post‐injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age‐matched controls from 20–30 d, 46–73 d, and 75–100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40–50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10–18 d post‐injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.