PMID- 2566592 OWN - NLM STAT- MEDLINE DCOM- 19890630 LR - 20190723 IS - 0021-8820 (Print) IS - 0021-8820 (Linking) VI - 42 IP - 5 DP - 1989 May TI - Selective killing of human T cell lymphotropic virus type I-transformed cell lines by a damavaricin Fc derivative. PG - 779-87 AB - n-Pentyl ether of damavaricin Fc (n-pentyl DvFc) preferentially killed human T-cell lymphotropic virus type I (HTLV-I)-transformed cell lines. The mechanism of action of the drug was investigated using MT-4 cells. Cytotoxic action was diminished by the removal of n-pentyl DvFc from the culture or by the addition of sulfhydryl compounds such as 2-mercaptoethanol and dithiothreitol. The killing activity of n-pentyl DvFc was also diminished by membrane-acting agents including quinidine and diphenylhydantoin. Influx and subsequent efflux of Ca2+ were observed when either HTLV-I infected (MT-4 cells) or uninfected cells were treated with n-pentyl DvFc. An efflux of K+ was observed in HTLV-I infected MT-4 cells immediately after the exposure of the cells to n-pentyl DvFc. The K+ efflux, however, was not observed in the uninfected T cells. n-Pentyl DvFc seems to act primarily on the cell surface of MT-4 cells, leading to the perturbation of membrane function. The restoration of cell growth, however, is critically dependent on the presence of dithiothreitol and 2-mercaptoethanol, implying a role for a free sulfhydryl group in the killing activity. FAU - Ito, S AU - Ito S AD - Shin-Etsu Chemical Co., Ltd., Tokyo. FAU - Yamamoto, N AU - Yamamoto N FAU - Nomoto, K AU - Nomoto K FAU - Sasaki, K AU - Sasaki K FAU - Onodera, K AU - Onodera K LA - eng PT - Journal Article PL - England TA - J Antibiot (Tokyo) JT - The Journal of antibiotics JID - 0151115 RN - 0 (Anti-Bacterial Agents) RN - 0 (Antiviral Agents) RN - 1404-74-6 (Streptovaricin) RN - 60-24-2 (Mercaptoethanol) RN - 6158TKW0C5 (Phenytoin) RN - 70940-04-4 (damavaricin Fc pentyl ether) RN - 9007-49-2 (DNA) RN - ITX08688JL (Quinidine) RN - RWP5GA015D (Potassium) RN - SY7Q814VUP (Calcium) RN - T8ID5YZU6Y (Dithiothreitol) SB - IM MH - Anti-Bacterial Agents MH - Antiviral Agents/*pharmacology/therapeutic use MH - Calcium/metabolism MH - Cell Line, Transformed MH - Cell Membrane/drug effects/metabolism MH - Cell Membrane Permeability/drug effects MH - Cell Survival/drug effects MH - Cell Transformation, Neoplastic MH - Cell Transformation, Viral MH - DNA/biosynthesis MH - Dithiothreitol/pharmacology MH - *Human T-lymphotropic virus 1 MH - Humans MH - Leukemia, T-Cell/drug therapy/pathology MH - Mercaptoethanol/pharmacology MH - Phenytoin/pharmacology MH - Potassium/metabolism MH - Quinidine/pharmacology MH - Streptovaricin/*pharmacology/therapeutic use MH - T-Lymphocytes/*drug effects/metabolism/microbiology EDAT- 1989/05/01 00:00 MHDA- 1989/05/01 00:01 CRDT- 1989/05/01 00:00 PHST- 1989/05/01 00:00 [pubmed] PHST- 1989/05/01 00:01 [medline] PHST- 1989/05/01 00:00 [entrez] AID - 10.7164/antibiotics.42.779 [doi] PST - ppublish SO - J Antibiot (Tokyo). 1989 May;42(5):779-87. doi: 10.7164/antibiotics.42.779.