-transparent.png){kind=logo}
Covalent binding of 3H-labeled VP 16-213 to rat liver and HeLa cell microsomal proteins was studied in vitro. Metabolic activation by cytochrome P-450 was found to play a role in the covalent binding of VP 16-213 to rat liver microsomal proteins, as shown by the need of NADPH cofactor, the increased binding after phenobarbital pretreatment and the inhibition by SFK-525A. Addition of ascorbic acid or alpha-phenyl-N-tert. butylnitrone to the incubation mixture depressed covalent binding by about 85%, suggesting that formation of a reactive metabolite from the phenolic structure may be involved in the binding process. VP 16-213 did not inhibit aminopyrine N-demethylase at the concentration used in the binding experiments (17 microM), indicating that metabolism of its methylenedioxy group does not play a role in binding to microsomal proteins. HeLa cell microsomes were found to possess aminopyrine N-demethylase activity. Covalent binding of radiolabeled VP 16-213 to HeLa cell microsomes decreased by about 64% if NADPH was omitted.
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
February 1987,
Biochemical pharmacology,
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
March 1978,
Molecular pharmacology,
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
January 1981,
Advances in experimental medicine and biology,
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
April 1984,
Biokhimiia (Moscow, Russia),
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
June 1992,
Biochemical pharmacology,
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
July 1985,
Biochemical pharmacology,
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
December 1987,
Archives of toxicology,
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
February 1978,
Biochemical pharmacology,
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
May 1987,
Archives of biochemistry and biophysics,
J M van Maanen, and
C de Ruiter, and
J de Vries, and
P R Kootstra, and
F Gobas, and
H M Pinedo
October 1989,
Biochemical pharmacology,
