Alpha-naphthylisothiocyanate cytotoxicity in hepatocytes and other cultured cells
- Michigan State Univ., East Lansing (United States)
Alpha-naphthylisothiocyanate (ANIT) is a model hepatotoxicant that causes injury to liver parenchymal and bile ductular cells in vivo. In this study, toxicity to various cells in culture was evaluated. In short term cultures of rat hepatocytes (HCs), a 4hr exposure to ANIT caused a concentration dependent increase in cytotoxicity as measured by lactate dehydrogenase (LDH) release. HCs cultured for 24hr or longer demonstrated a delay in ANIT-induced LDH release when compared to 2.5hr cultures. In addition, the magnitude of the cytotoxic response was greater in longer term cultures. The threshold for ANIT-induced cytotoxicity in HCs was between 20 and 63uM. In porcine endothelial cell cultures, ANIT cytotoxicity was similar to that seen in HCs. In two transformed cells lines, the Swiss 3T3 fibroblast and WB cell, a 24hr exposure to ANTI caused a concentration dependent increase in LDH release. Like the HCs, the threshold concentration was between 20 and 63uM. These results indicate that ANIT is directly cytotoxic to various cells in culture. Since endothelium and fibroblasts are deficient in cytochrome P-450 mixed function oxidase activity, ANIT toxicity in culture may be largely independent of this xenobiotic metabolizing system.
- OSTI ID:
- 5265402
- Report Number(s):
- CONF-9104107--
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Vol. 5:4; ISSN FAJOE; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BODY
CELL CULTURES
CONNECTIVE TISSUE CELLS
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
ENDOTHELIUM
ENZYME ACTIVITY
ENZYMES
FIBROBLASTS
HEMIACETAL DEHYDROGENASES
ISOCYANATES
LACTATE DEHYDROGENASE
LIVER CELLS
MAMMALS
METABOLISM
MICE
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATHOLOGICAL CHANGES
PROTEINS
RATS
RODENTS
SOMATIC CELLS
SWINE
TISSUES
TOXICITY
VERTEBRATES