Acetaminophen metabolism, cytotoxicity, and genotoxicity in rat primary hepatocyte cultures
Journal Article
·
· Toxicol. Appl. Pharmacol.; (United States)
Acetaminophen (APAP) metabolism, cytotoxicity, and genotoxicity were measured in primary cultures of rat hepatocytes. Although 3 mM APAP caused a slight increase in cellular release of lactate dehydrogenase into the culture medium, cellular glutathione concentration (an index of APAP metabolism) was reduced by 50%. APAP at 7 mM was significantly more toxic to these hepatocytes and had a similar but more marked effect on glutathione concentrations. In spite of its cytotoxicity, neither dose of APAP stimulated DNA repair synthesis when monitored by the rate of incorporation of (/sup 3/H)thymidine into DNA following exposure to APAP. Thus, although APAP has been shown to be both hepato- and nephrotoxic in several in vivo and in vitro systems, the reactive toxic metabolite of APAP is not genotoxic in rat primary hepatocyte cultures.
- OSTI ID:
- 5075072
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 2; ISSN TXAPA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550501 -- Metabolism-- Tracer Techniques
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIPYRETICS
AZINES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL CULTURES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DNA
DNA REPAIR
DRUGS
ENZYME ACTIVITY
ENZYMES
GLUTATHIONE
HEMIACETAL DEHYDROGENASES
HETEROCYCLIC COMPOUNDS
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LACTATE DEHYDROGENASE
LIVER CELLS
MAMMALS
METABOLISM
METABOLITES
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PEPTIDES
POLYPEPTIDES
PROTEINS
PYRIMIDINES
RADIOPROTECTIVE SUBSTANCES
RATS
RECOVERY
REPAIR
RIBOSIDES
RODENTS
SOMATIC CELLS
THYMIDINE
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIPYRETICS
AZINES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL CULTURES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DNA
DNA REPAIR
DRUGS
ENZYME ACTIVITY
ENZYMES
GLUTATHIONE
HEMIACETAL DEHYDROGENASES
HETEROCYCLIC COMPOUNDS
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LACTATE DEHYDROGENASE
LIVER CELLS
MAMMALS
METABOLISM
METABOLITES
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PEPTIDES
POLYPEPTIDES
PROTEINS
PYRIMIDINES
RADIOPROTECTIVE SUBSTANCES
RATS
RECOVERY
REPAIR
RIBOSIDES
RODENTS
SOMATIC CELLS
THYMIDINE
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES