Abstract
The antitumor agent VP-16-213 is oxidatively O-demethylated by rat liver microsomes and purified rat liver microsomal P-450. 3-Methylcholanthrene can quantitatively induce O-demethylation of VP-16-213. The K(m) and V(max) values for O-demethylation by noninduced, phenobarbital-, and 3-methylcholanthrene-induced rat liver microsomes were found to be 130, 600, and 160 μM and 8.5, 11.8, and 15.6 nmol H2CO/min·mg protein, respectively. Mass spectrometric comparison of the product of O-demethylation of VP-16-213 with the synthetic metabolite resulted in identification of the orthodihydroxy derivative. In studies on the biological activity of the orthodihydroxy derivative, it was found to inactivate single- and double-stranded ΦX174 DNA, to bind to calf thymus DNA and to be highly toxic against chinese hamster ovary cells.
Original language | English (US) |
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Pages (from-to) | 4658-4662 |
Number of pages | 5 |
Journal | Cancer Research |
Volume | 47 |
Issue number | 17 |
State | Published - 1987 |
Externally published | Yes |
ASJC Scopus subject areas
- Cancer Research
- Oncology