This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Williams, M. T. Articles by Cory, J. G. Search for Related Content PubMed PubMed Citation Articles by Williams, M. T. Articles by Cory, J. G.

Liver Microsomal Inactivation of 4-Methyl-5-amino-1-formylisoquinoline Thiosemicarbazone as an Inhibitor of Ribonucleotide Reductase¹

Departments of Biochemistry [M.T.W.,L.S.], and Internal Medicine [A.H.C.,J.G.C], University of South Florida, College of Medicine, Tampa, florida 33612

Studies were carried out to determine the effects of preincubation of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ) with hepatic microsomes on the ability of MAIQ to inhibit CDP reductase activity in vitro. An aliquot from the 100,000 x g supernatant fraction from this incubation was used in the CDP reductase assay. MAIQ incubated in the absence of microsomes inhibited CDP reductase activity in a dose-dependent manner. At high MAIQ concentration (5 µM) CDP reductase activity was inhibited 95%. When MAIQ (5 µM) was first incubated in the presence of hepatic microsomes and NADPH, CDP reductase activity was inhibited only 30%. This attenuation of MAIQ inhibition was dependent on time of incubation and microsomal protein concentration and showed an obligatory requirement for NADPH or NADH. Significant attenuation was observed at pyridine nucleotide concentrations as low as 0.1 mM. Heat denaturation of microsomal proteins inactivated their ability to attenuate the MAIQ inhibition. Microsomes prepared from Ehrlich tumor cells were ineffective as inactivators of MAIQ.

Results of our studies show that hepatic microsomes contain an enzyme(s) which can inactive MAIQ as an inhibitor of CDP reductase.

¹ This research was supported by Grant CA 27398 from the National Cancer Institute, USPHS.

² To whom requests for reprints should be addressed, at Department of Biochemistry, MDC Box 7, USF College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612.

³ Present address: Division of Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

Received 4/ 8/88. Revised 7/22/88. Accepted 8/15/88.