Promotive action of acylated ascorbate on cellular DNA synthesis and growth at low doses in contrast to inhibitory action at high doses or upon combination with hyperthermia.
Effects of 6-O-palmitoyl ascorbate (ascorbate) developed to increase the antitumour activity of ascorbic acid on DNA synthesis and proliferation of Ehrlich ascites tumour cells were investigated. Treatment of the cells with the acylated ascorbate at 25-50 microM for 1 h resulted in no effect on DNA synthesis, assayed by pulse incorporation of [3H]thymidine after a culture period of 20 h, but led to 49%-87% enhanced DNA synthesis after 4 days, suggesting that long-term culture is required for promotion by ascorbate to occur. At a dose as high as 75 microM acylated ascorbate, however, cellular DNA synthesis was 64% inhibited after 20 h and 99% after 4 days. The results suggest that acylated ascorbate exhibits a dual action on DNA synthesis: promotion at low doses and inhibition at high doses, both of which are potentiated in a time-dependent manner. In contrast to the above-mentioned results at 37 degrees C, acylated ascorbate at 25-75 microM inhibited but did not promote DNA synthesis at 42 degrees C whatever the culture period. Similar results were exhibited when proliferation of cells cultured for a long period was investigated. At 37 degrees C, 50 microM acylated ascorbate increased the number of the cells to 3.6 times the control values after 8 days and to 1.9 times after 11 days; in contrast, a 75-microM dose decreased the cell number considerably. Combination with hyperthermia (42 degrees C) suppressed the increase and cell growth was completely inhibited at 75 microM.
Kageyama
K
K
Radioisotope Centre, Osaka City University Medical School, Japan.
Onoyama
Y
Y
Otani
S
S
Kimura
M
M
Matsui-Yuasa
I
I
Nagao
N
N
Miwa
N
N
D000215:Acylation; D000818:Animals; D016587:Antimutagenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D005260:Female; D006358:Hot Temperature; D051379:Mice; D008813:Mice, Inbred ICR; D014407:Tumor Cells, Cultured
D016587:Antimutagenic Agents; D004273:DNA, Neoplasm; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid