NDLI: Characterization of the human hepatocellular carcinoma (HEPG2) cell line as an in vitro model for cadmium toxicity studies

Content Provider	Springer Nature Link
Author	Dehn, P. F. White, C. M. Conners, D. E. Shipkey, G. Cumbo, T. A.
Copyright Year	2004
Abstract	Biochemical indicators and in vitro models, if they mimic in vivo responses, offer potentially sensitive tools for inclusion in toxicity assessment programs. The purpose of this study was to determine whether the HepG2 cell line would mimic known in vivo or in vitro (or both) responses of mammalian systems when confronted with cadmium (Cd$^{2+}$). Uptake and compartmentalization of Cd$^{2+}$, metallothionein (MT) compartmentalization, and glutathione (GSH) depletion were examined. In addition, several cytotoxic and stress effects, e.g., viability (neutral red [NR] uptake, 3-[4,5-dimethylthiozole-2-yl]-2,5,-biphenyl tetrazolium bromide [MTT] dye conversion, and live/dead [L/D]), membrane damage (lactate dehydrogenase leakage), metabolic activity (adenosine triphosphate levels), and detoxification capabilities (GSH content, cytochrome P4501A1/2 [EROD (ethoxyresorufin-o-deethylase)] activity, and MT induction), were measured in both naive (no previous exposure) and Cd$^{2+}$ preexposed cells. Cadmium uptake increased during a 24-h period. Metallothionein induction occurred in response to both Cd$^{2+}$ and ZnCl$_{2}$; however, Cd$^{2+}$ was the more potent inducer. Both Cd$^{2+}$ and MT were localized primarily in the cytoplasmic compartment. All biochemical responses, except EROD, showed concentration—response relationships, after 24-h exposure to Cd$^{2+}$ (ranges 0–3 ppm [26.7 μM]). Cadmium effects were reduced in preexposed cells, indicating adaptive tolerance or increased resistance had occurred. Twenty-four-hour LC$_{50}$, dose causing death of 50% of the test subjects, values were 0.97, 0.69, and 0.80 ppm (8.7, 6.2, and 7.2 μM) for naive cells and 1.45, 1.21, and 1.39 ppm (12.9, 10.7, and 12.3 μM) for preexposed cells based on the NR, MTT, and L/D assays, respectively. These data indicate that this carcinoma cell line is a useful in vitro model for cadmium toxicity studies.
Starting Page	172
Ending Page	182
Page Count	11
File Format	PDF
ISSN	10712690
Journal	In Vitro Cellular & Developmental Biology - Animal
Volume Number	40
Issue Number	5-6
e-ISSN	1543706X
Language	English
Publisher	Springer-Verlag
Publisher Date	2004-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	tolerance cytotoxicity biochemical indicators metals Cell Biology Developmental Biology Animal Genetics and Genomics Animal Biochemistry Animal Physiology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine

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