title: Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). II. Hydrolysis by tissue homogenates and drug uptake by tumor cells in vitro.
abstract: 1-(2-Chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077) was hydrolyzed to its glucosyl metabolite TA-G by homogenates of guinea pig organs, rabbit VX-2 carcinoma and rat Yoshida sarcoma. The rate of TA-G formation by the kidney was the highest among the tissues examined and that by the diluted blood was undetectably low, reflecting their maltase activities. TA-077 was also hydrolyzed by suspensions of Yoshida sarcoma, AH130 hepatoma, L1210 leukemia, P388 leukemia and DBLA-10/C leukemia cells. The rate of TA-G formation was increased 10 fold by homogenizing the tumor cells. TA-G was taken up by the tumor cells much more efficiently than TA-077, explaining the higher sensitivities of the cultured tumor cells to TA-G than to TA-077. However, neither the maltase activity nor the membrane permeability to the drugs was a factor influential enough to explain the differences in drug sensitivity among the tumor cell lines.
authors.affiliation: Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hayashida
authors.forename: K
authors.initials: K
authors.lastname: Oda
authors.forename: Y
authors.initials: Y
authors.lastname: Akaike
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.forename: S
authors.initials: S
authors.lastname: Takeyama
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D065089:Glycoside Hydrolase Inhibitors; D006168:Guinea Pigs; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D009607:Nitrosourea Compounds / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D014407:Tumor Cells, Cultured / Q000378:metabolism*; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D065089:Glycoside Hydrolase Inhibitors; D009607:Nitrosourea Compounds; C035789:TA 077; D000520:alpha-Glucosidases