Reduced cadmium-induced cytotoxicity in cultured liver cells following 5-azacytidine pretreatment

Journal Article · Fri Nov 01 04:00:00 EST 1985 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(85)90161-9· OSTI ID:6033781

Waalkes, M P; Wilson, M J; Poirier, L A

Recent work indicated that administration of the pyrimidine analog 5-azacytidine (AZA), either to cells in culture or to rats, results in an enhancement of expression of the metallothionein (MT) gene. Since MT is thought to play a central role in the detoxification of cadmium, the present study was designed to assess the effect of AZA pretreatment on cadmium cytotoxicity. Cultured rat liver cells in log phase of growth were first exposed to AZA (8 microM). Forty-eight hours later, cadmium was added. A modest increase in MT amounts over control was detected after AZA treatment alone. Cadmium alone resulted in a 10-fold increase in MT concentrations. The combination of AZA pretreatment followed by cadmium exposure caused a 23-fold increase in MT concentrations over control. Treatment with the DNA synthesis inhibitor hydroxyurea (HU) eliminated the enhancing effect of AZA pretreatment on cadmium induction of MT, indicating that cell division is required. AZA-pretreated cells were also harvested and incubated in suspension with cadmium for 0 to 90 min. AZA-pretreated cells showed marked reductions in cadmium-induced cytotoxicity as reflected by reduced intracellular potassium loss, glutamic-oxaloacetic transaminase loss, and lipid peroxidation following cadmium exposure. Results suggest that AZA pretreatment induces tolerance to cadmium cytotoxicity which appears to be due to an increased capacity to synthesize MT rather than high quantities of preexisting MT at the time of cadmium exposure.

• Research Organization: National Cancer Institute, MD
• OSTI ID: 6033781
• 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

Related Subjects

550201 -- Biochemistry-- 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.
ALKALI METALS
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
CADMIUM
DNA
ELEMENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
LABELLED COMPOUNDS
LIVER CELLS
MAMMALS
METALLOPROTEINS
METALLOTHIONEIN
METALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
POTASSIUM
PROTEINS
PYRIMIDINES
RATS
RIBOSIDES
RODENTS
SOMATIC CELLS
SYNTHESIS
THYMIDINE
TOXICITY
TRITIUM COMPOUNDS
URACILS
URIDINE
VERTEBRATES