Development of a cytochrome P-450 monooxygenase system in clonogenic hemopoietic cells

We characterized the presence of the monooxygenase arylhydrocarbon-hydroxylase (AHH), in mouse bone marrow cells taken directly from animals and from bone marrow colony culture. Using a standard radio-isotopic assay it was found that AHH activity was present in mouse bone marrow cells and that there was demonstratable activity in preparations taken directly from differentiated erythroid and myeloid colony cultures. Murine colonies of erythroid (CFU-E) and granulocytes (CFU-GM) were grown and AHH activity determined in non-induced and 3-methylcholanthrene (3-MC) induced cultures. Addition of 3-MC to erythropoietin dependent CFU-E was found to induce AHH activity above controls in a dose dependent manner, with 75 micrograms generating a maximal effect. CFU-E taken from different incubation periods (1-4 days) revealed that AHH was maximal in 2 1/2 day cultures and thereafter declined. In contrast, maximal AHH activity was obtained from 6-7 day CFU-GM and 40 micrograms of 3-MC stimulated the activity by 88%. These results demonstrate that AHH is present in normal mouse bone marrow cells and developing hemopoietic colonies, and that induction of AHH may indicate an important role for these cytochrome P-450 monooxygenases in cell development and differentiation as well as in the metabolism of various drugs.