Metabolic alpha-hydroxylation of N-nitrosomorpholine and 3,3,5,5-tetradeutero-N-nitrosomorpholine in the F344 rat

Journal Article · Tue Dec 01 04:00:00 EST 1981 · Cancer Res.; (United States)

OSTI ID:5405396

Hecht, S S; Young, R

The metabolism of N-nitrosomorpholine and of of 3,3,5,5-tetradeutero-N-nitrosomorpholine was studied in male F344 rats. The latter is less carcinogenic and less mutagenic than is N-nitrosomorpholine. alpha-Hydroxylation (3- or 5-hydroxylation) of N-nitrosomorpholine by liver microsomes and a reduced nicotinamide adenine dinucleotide phosphate-generating system produced (2-hydroxyethoxy)acetaldehyde, which was identified as its 2,4-dinitrophenylhydrazone derivative. When we administered N-nitrosomorpholine to rats i.p., we did not detect (2-hydroxyethoxy)acetaldehyde in the urine, but we did identify (2-hydroxyethoxy)acetic acid (16% of the dose). We also identified N-nitroso(2-hydroxyethyl)glycine (33% of the dose) from beta-hydroxylation (2- or 6-hydroxylation), N-nitrosodiethanolamine (12%), and unchanged N-nitrosomorpholine (1.5%) in the urine. The deuterated analogs of the above metabolites were isolated from the urine of rats treated with 3,3,5,5-tetradeutero-N-nitrosomorpholine in yields as follows: (2-hydroxyethoxy)acetic acid (3.4%); N-nitroso(2-hydroxyethyl)glycine (37%); N-nitrosodiethanolamine (12%); N-nitrosomorpholine (0.4%). These data demonstrates that deuterium substitution in the alpha-positions of N-nitrosomorpholine caused a decrease in the extent of alpha-hydroxylation and indicate that alpha-hydroxylation is the mechanism of activation of N-nitrosomorpholine.

• Research Organization: Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, New York
• OSTI ID: 5405396
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 41:12 Pt 1; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CARCINOGENESIS
CELL CONSTITUENTS
COENZYMES
DEUTERIUM COMPOUNDS
DIGESTIVE SYSTEM
ETHERS
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXYLATION
LIVER
MAMMALS
MATERIALS
METABOLIC ACTIVATION
METABOLISM
MICROSOMES
MORPHOLINES
MUTAGENESIS
NADP
NITROSO COMPOUNDS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
PATHOGENESIS
RATS
RODENTS
URINE
VERTEBRATES
WASTES