Enhanced metallothionein gene expression is associated with protection from cadmium-induced genotoxity in cultured rat liver cells

Journal Article · Sat Jan 01 04:00:00 EST 1994 · Journal of Toxicology and Environmental Health; (United States)

OSTI ID:7104348

Coogan, T P; Bare, R M; Bjornson, E J; Waalkes, M P ^[1]

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1. National Cancer Institute, Frederick, MD (United States)

Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that appear to play an important role in the cellular defense system against cadmium toxicity. Although substantial evidence exists demonstrating a reduction in cadmium toxicity concomitant with MT induction, little is known about the possible effects of stimulation of MT synthesis on cadmium-induced genotoxicity. Thus, the alkaline elution technique was used to assess single-strand DNA damage (SSD) in TRL-1215 cells, a liver-derived cell line shown to have inducible MT Gene expression. The SSD accumulated over a 2-h time period in a time-dependent manner following exposure to 500 [mu]M CdCl[sub 2]. Low concentration cadmium pretreatment (10 [mu]M CdCl[sub 2], 24 h) provided protection against the genotoxicity of high-concentration cadmium (500 [mu]M CdCl[sub 2], 2 h). A 2-h exposure to 500 [mu]M CdCl[sub 2], had no effect on viability, as assessed using a tetrazolium-dye based assay, in cells from either the pretreated or nonpretreated group. Metallothionein was induced in a time-dependent manner by low-concentration cadmium pretreatment: Exposure for 24 and 48 h resulted in 3.3- and 6.4-fold increases, respectively. In addition, a 24-h exposure to low-concentration cadmium resulted in an increase in MT-I gene expression. Cadmium accumulation was 2.6-fold greater in low-concentration cadmium-pretreated cells as compared to non-pretreated cells. These data demonstrate that low-concentration cadmium pretreatment provides protection against cadmium-induced single-strand DNA damage and support the hypothesis that this protection is due to stimulation of MT gene expression. 38 refs., 6 figs.

• OSTI ID: 7104348
• Journal Information: Journal of Toxicology and Environmental Health; (United States), Journal Name: Journal of Toxicology and Environmental Health; (United States) Vol. 41:2; ISSN 0098-4108; ISSN JTEHD6
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOLOGICAL EFFECTS
CADMIUM
DAMAGE
DNA
ELEMENTS
GENE AMPLIFICATION
GENETIC EFFECTS
LIVER CELLS
METALLOPROTEINS
METALLOTHIONEIN
METALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RESPONSE MODIFYING FACTORS
SOMATIC CELLS
TOXICITY