Inhibition of DNA synthesis by alpha-1-antichymotrypsin.
The effect of alpha-1-antichymotrypsin (ACT), which is known as an efficient serum protease inhibitor and is detected in tumor cell nuclei, on DNA synthesis was studied. ACT inhibited the activity of DNA polymerase alpha purified from human stomach adenocarcinoma. Other human serum proteins including serum albumin, alpha-1-acidglycoprotein, alpha-1-antitrypsin, and immunoglobulin G, as well as other protease inhibitors, such as leupeptin, pepstatin, PMSF and chymostatin, did not affect the activity of DNA polymerase alpha. It was therefore concluded that the inhibitory action of ACT on DNA polymerase alpha was direct phenomenon unrelated to its protease inhibitory activity. Furthermore, the effect of ACT on DNA synthesis was also studied using lysolecithin-permeabilized cultured human stomach carcinoma cells. ACT added in the medium inhibited DNA synthesis and the degree of inhibition depended on incubation time. It was proportional to ACT concentration and the concentration of ACT required for 50% inhibition was 0.8 mg/ml.
Tsuda
M
M
Department of Biochemistry, School of Medicine, Tokai University, Kanagawa, Japan.
Umezawa
Y
Y
Masuyama
M
M
Nozaki
S F
SF
Yamaguchi
K
K
Katsunuma
T
T
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D000514:alpha 1-Antichymotrypsin / Q000494:pharmacology*
D004273:DNA, Neoplasm; D008244:Lysophosphatidylcholines; D000514:alpha 1-Antichymotrypsin; D004257:DNA Polymerase II