Role of cytochrome P-450 isozyme 3a in microsomal metabolism of three nasal carcinogens
Cytochrome P-450 isozyme 3a, first isolated from rabbit liver microsomes, also occurs in nasal mucosal microsomes. The role of the cytochrome in the metabolism of three nasal carcinogens, hexamethylphosphoramide (HMPA), N-nitrosodiethylamine (NDEA), and phenacetin (PA) was examined in the present study. Microsomal preparations from rabbit nasal ethmoturbinates catalyze the O- or N-deakylation of the above compounds at much greater rates than do liver microsomes. The participation of isozyme 3a was shown by immunochemical experiments involving inhibition by anti-isozyme 3a antibodies. With 1.0 mM substrate present, anti-3a IgG inhibited the activities in nasal membrane microsomes as follows: HMPA N-demethylation, 61%; NDEA N-deethylation, 67%; and PA O-deethylation, 75%. Similar results were obtained in experiments with liver microsomes except for PA O-deethylation, which was only slightly inhibited (18%) by the antibody. The involvement of isozyme 3a in the dealkylation activities was further indicated by a correlation between the increase in anti-3a-inhibited rates and the induction of isozyme 3a in liver microsomes from animals chronically administered ethanol. They conclude that isozyme 3a plays a significant role in the metabolism and, presumably, the known carcinogenicity of HMPA, NDEA, and PA in nasal mucosa.
- Research Organization:
- Univ. of Michigan, Ann Arbor
- OSTI ID:
- 7145085
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETOPHENETIDIN
ALCOHOLS
AMIDES
AMINES
ANALGESICS
ANIMALS
ANTIBODIES
ANTIPYRETICS
BIOCHEMICAL REACTION KINETICS
BODY
BODY AREAS
CARCINOGENS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL REACTIONS
DEALKYLATION
DIGESTIVE SYSTEM
DRUGS
ETHANOL
FACE
GLANDS
HEAD
HYDROXY COMPOUNDS
KINETICS
LIVER
MAMMALS
MEMBRANES
METABOLISM
MICROSOMES
MUCOUS MEMBRANES
NITROSAMINES
NITROSO COMPOUNDS
NOSE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PROTEINS
RABBITS
REACTION KINETICS
RESPIRATORY SYSTEM
VERTEBRATES