Affordable Access

Publisher Website

Binding of nitrosamines to cytochromeP-450 of liver microsomes

Authors
Journal
Chemico-Biological Interactions
0009-2797
Publisher
Elsevier
Publication Date
Volume
28
Issue
1
Identifiers
DOI: 10.1016/0009-2797(79)90111-x
Disciplines
  • Biology
  • Chemistry

Abstract

Abstract The interactions of 5 carcinogenic and 1 non-carcinogenic nitrosamines with hepatic microsomal cytochrome (cyt.) P-450 were investigated, using both optical difference and electron paramagnetic resonance (EPR) spectroscopic methods. Liver microsomes from phenobarbital (PB)-pretreated mice and 3-methylcholanthrene (3-MC)-pretreated rats were used, in order to have an increased specific content of cyt. P-450 and cyt. P-448 respectively. The optical and EPR spectral data obtained in the oxidised state suggest that nitrosamines are able to bind both as substrates and as ligands to the hemoprotein cyt. P-450, depending on the concentration of nitrosamine, its chemical identity and the cytochrome species present. After reduction with dithionite or NADPH in the optical difference spectrum a Soret band developed between 444 and 453 nm to an extent, which is dependent on the particular nitrosamine present. This initial nitrosamine-induced spectrum might represent a ferrous nitric oxide (NO)-cyt. P-450 complex. It appears unstable and is converted kinetically into a spectrum lacking a Soret band, but with a predominant absorbance minimum at about 425 nm. A visible band is located at 585 nm. In the EPR spectrum a sharp 3-line signal around g = 2.01 appears concomitantly. Both spectral parameters are typical of a NO-cyt. P-420 complex. These results, in conjunction with metabolic studies, indicate that nitrosamines are denitrosated by a reductive process in which cyt. P-450 appears to be involved. The resulting NO-cyt. P-450 complex denatures to a NO-cyt. P-420 complex when the dioxygen level is not sufficiently high to compete successfully.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments

More articles like this

Binding of nitrosamines to cytochrome P-450 of liv...

on Chemico-Biological Interaction... 1979

Cloning and expression of koala (Phascolarctos cin...

on Comparative Biochemistry and P... Jan 01, 2009

20β-hydroxy-C21-steroid 20β-oxidase activity of cy...

on Biochimica et Biophysica Acta... Jan 01, 1998

In vivoadministration of H2blockers, cimetidine an...

on International Journal of Bioch... Jan 01, 1994
More articles like this..