EFFECTS OF DIFFERENTIATION-INDUCING AGENTS ON PURINE NUCLEOTIDE-METABOLISM IN AN OVARIAN-CANCER CELL-LINE

The effects of the differentiation-inducing agents sodium butyrate (Na OBt), dimethylsulfoxide (DMSO) and mycophenolic acid (MA), on purine n ucleotide metabolism, was studied in an ovarian carcinoma cell line (G ZL-8). Exposure to these agents inhibited cell proliferation, but did not affect cell viability. Three hours following exposure, NaOBt and D MSO moderately decelerated purine synthesis de novo, but MA accelerate d it three-fold, this being associated with a two-fold increase in the excretion of hypoxanthine and xanthine into the incubation medium. Na OBt and DMSO did not affect the cellular nucleotide content, but MA ca used a 73% decrease in GTP content and about a 50% increase in the cel lular content of UTP. The following alterations in cellular enzyme act ivity were observed 72 h following exposure: NaOBt decreased the activ ity of hypoxanthine-guanine phosphoribosyltransferase and increased th e activity of IMP and of AMP 5'-nucleotidases, DMSO increased the acti vity of IMP 5'-nucleotidase, and MA increased the activity of the two nucleotidases. The results suggest that, in the carcinoma cell line st udied, the differentiation process induced by NaOBt and DMSO may be as sociated with a general shift in the direction of purine metabolism fr om anabolism to catabolism, whereas that induced by MA is associated w ith a specific decrease in the production of GTP.