Rat liver-mediated degradation of dibromodulcitol

• Published in: European journal of cancer & clinical oncology Vol. 21; no. 7; pp. 881 - 885
• Main Authors: Csetényi, J., Gáti, É., Hegedüs, L., Horváth, I.P., Holczinger, L.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.1985; New York, NY Pergamon Press
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; General aspects; Inactivation, Metabolic; Liver - enzymology; Liver - metabolism; Male; Medical sciences; Mitolactol - metabolism; NADP - metabolism; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Antineoplastic agent; Vertebrata; Mammalia; Rat; Animal; Liver; Rodentia; In vitro; Activity metabolism relation
• ISSN: 0277-5379
• DOI: 10.1016/0277-5379(85)90229-9

The rate and extent of dibromodulcitol (DBD) conversion by 9000 g rat liver supernatant with an NADPH-generating system (S-9 mix) were studied using 3 H-labelled drug. Results indicated that S-9 mix seemed to exert an initial protective effect delaying the solvolysis of DBD for about 30 min at 37°C followed by rapid degradation into exclusively pharmacologically inactive products. Thus S-9 mix contained merely DBD as an effective agent; it amounted to less than 40% of the total radioactive compounds by 120 min. In the control mixtures the sovolytically produced effective drug content, i.e. the sum of DBD, 1,2-anhydro-6-bromo-6-deoxygalactitol (BrEpG), 1,2–5,6-dianhydrogalactitol (DAG) was 63%. Our results suggest the involvement of liver enzymes in the detoxification of DBD into inactive products. Therefore the antitumour effect of DBD cannot be attributed to its active BrEpG and DAG alone. The drug in its unchanged form may contribute to a somewhat greater extent to its cytostatic action than was believed before.