Transformation, Growth Rate, and the Heme Biosynthetic Pathway in V-abl-Transfected Fibroblasts

The relationship between growth rate and various parameters of the heme biosynthetic pathway was studied in two cell lines of rat fibroblasts (REabl-1 and REabl-3) transfected with v-abl oncogene, coded by the Abelson murine leukemia virus, and subjected to glucocorticoid dependent transformation. In the REabl-1 cell line, whose growth rate was only slightly affected by dexamethasone (DX), almost no change was noticed either in heme content or in the enzymatic activities of aminolevulinate synthase (ALAS), porphobilinogen deaminase (PBGD), and ferrochelatase (FC) in the presence of various concentrations of DX. In the REabl-3 cell line, exhibiting a growth rate highly sensitive to DX, a significant reduction in intracellular heme concomitantly with decreases in ALAS and FC activities and a threefold increase in PBGD were noted. The fact that incubation with 10⁻⁵M hemin did not result in a decrease in ALAS activity raised the possibility that REabl cells lack a negative feedback control mechanism. The relationships between transformation, growth rate, and heme biosynthetic pathway are discussed.