Further studies of the metabolic incorporation and covalent binding of inhaled (/sup 3/H)- and (/sup 14/C)formaldehyde in Fischer-344 rats: effects of glutathione depletion

Journal Article · Mon Jun 15 04:00:00 EDT 1987 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(87)90181-5· OSTI ID:6326803

Casanova, M; Hd', Heck

Glutathione (GSH) is required for the oxidation of formaldehyde (HCHO) to formate catalyzed by formaldehyde dehydrogenase (FDH). The effects of GSH depletion on the mechanisms of labeling of macromolecules in the rat nasal mucosa and bone marrow by /sup 3/HCHO and H/sup 14/CHO were investigated. Male rats were exposed for 3 hr to atmospheres containing /sup 3/HCHO and H/sup 14/CHO at concentrations of 0.9, 2, 4, 6, or 10 ppm, 1 day after a single 3-hr preexposure to the same concentration of unlabeled HCHO. Two hours prior to the second exposure, the animals were injected either with phorone (300 mg/kg, ip) or with corn oil. The concentration of nonprotein sulfhydryls in the nasal respiratory mucosa of phorone-injected rats was decreased to 10% of that of corn oil-injected rats. The metabolic incorporation of /sup 3/HCHO and H/sup 14/CHO into DNA, RNA, and proteins in the respiratory and olfactory mucosa and bone marrow (femur) was significantly decreased, and DNA-protein crosslinking was significantly increased in the respiratory mucosa of phorone-injected relative to corn oil-injected rats at all HCHO concentrations. DNA-protein crosslinks were not detected in the respiratory mucosa of corn oil-injected rats at 0.9 ppm. Evidence was obtained for the formation of adducts of HCHO with the RNA from the nasal respiratory mucosa of phorone-injected rats at concentrations above 0.9 ppm. Covalent binding of HCHO to macromolecules in the bone marrow was not detected. These results indicate that the GSH-dependent oxidation of HCHO catalyzed by FDH is an important defense mechanism against the covalent reactions of HCHO with nucleic acids in the respiratory mucosa.

• Research Organization: Chemical Industry Institute of Toxicology, Research Triangle Park, NC
• OSTI ID: 6326803
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 1; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ALDEHYDES
ANIMAL TISSUES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BODY
BONE MARROW
CARBON 14 COMPOUNDS
COVALENCE
DNA
DNA ADDUCTS
DRUGS
ENZYME ACTIVITY
ENZYMES
FORMALDEHYDE
FUNCTIONS
GLUTATHIONE
HEMATOPOIETIC SYSTEM
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
METABOLISM
MUCOUS MEMBRANES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RESPIRATORY SYSTEM
RNA
RODENTS
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES