Autoradiographic analysis of proliferative activity in rat kidney epithelial and mesenchymal cell subpopulations following a carcinogenic dose of dimethylnitrosamine.

In a system that yields 100% incidence of renal mesenchymal tumors and a 30 to 40% incidence of renal cortical epithelial neoplasms, the proliferative activity of renal epithelial and mesenchymal cell subpopulations following a single dose of dimethylnitrosamine (DMN) was traced by autoradiographic analysis of [methyl-3H]thymidine uptake during the 3 weeks immediately posttreatment. The initial response to DMN was a depression in DNA synthesis and mitosis to near 0 levels in all segments of the nephron and in attendant mesenchymal cells for a period of 1 to 3 days. Following the period of inhibition, increased DNA synthetic activity was observed in certain subpopulations of both epithelium and mesenchyme and these patterns were matched by equivalent mitotic activity. A stimulation of DNA synthesis was observed in cells of the proximal and distal tubules of Zones 1 and 2 but in no other epithelial segments. The increased activity was most intense in Zone 1 epithelium reaching a peak at the 10th day after DMN injection 4 days after epithelial cell necrosis had commenced. In renal mesenchyme, the major response involved only the interstitial cells of Zones 1 and 2. At Day 3, there was a wave of increased DNA-synthetic and mitotic activity in the free interstitial cells of the cortex, followed by a 2nd, more intense peak of activity at Day 6. The cells responding at Day 3 appeared to involve the resident population of cortical fibrocytes while the major contribution to the Day 6 peak came from infiltrating mononuclear inflammatory cells, although resident fibrocytes and capillary endothelium also contributed. A significant wave of increased activity involved the intestitial cells of Zone 2, but the peak, although of equivalent intensity to the response in Zone 1, was single and occurred 3 days later at Day 9. Apart from a small, brief, and variable wave of activity in interstitial cells of Zone 3 from Days 8 to 10, no toerh mesenchymal cell populations in the kidney were stimulated by the injection of DMN.