Author/Editor		Fatur, T; Tušek, M; Falnoga, I; Ščančar, J; Lah, TT; Filipič, M
Title		DNA damage and metallothionein synthesis in human hepatoma cells (HepG2) exposed to cadmium
Type		članek
Source		Food Chem Toxicol
Vol. and No.		Letnik 40, št. 8
Publication year		2002
Volume		str. 1069-76
Language		eng
Abstract		Cadmium is an important heavy metal environmental toxicant, which is classified as a human carcinogen. The comet assay was used to evaluate the levels of DNA damage in a metabolically competent HepG2 cell line after treatment with low, non-cytotoxic and physiologically relevant concentrations of cadmium, alone and in combination with the dietary mutagen 2-amino-3-methylimidazo(4,5 f)quinoline (IQ) and with the environmental mutagen benzo(a)pyrene (B(a)P). After exposure of the cells to 10, 100 and 1000 nM CdCl2, a dose- and time-dependent increase of DNA damage was detected. Maximal damage was found after 12 h of treatment, but declined with further incubation with CdCl2. The increased synthesis of metallothioneins on exposure to CdCl2 up to 12 h suggests that they are responsible for the adaptation of HepG2 cells to the DNA damaging effects of CdCl2. Co-treatment of the cells with CdCl2 (10-1000 nM) and IQ (300 microM) induced a dose-dependent increase of DNA damage compared to cells treated with IQ alone. Corgenotoxic activity was also observed by increased formation of micronuclei in cells exposed to IQ and 1000 nM CdCl2; at this concentration, CdCl2 alone also induced micronuclei in HepG2 cells. Our results support the hypothesis that direct and indirect mechanisms are involved in cadmium-induced DNA damage.
Descriptors		CADMIUM CARCINOGENS DNA DAMAGE METALLOTHIONEIN ADAPTATION, PHYSIOLOGICAL BENZO(A)PYRENE CARCINOMA, HEPATOCELLULAR CELL SURVIVAL DOSE-RESPONSE RELATIONSHIP, DRUG LIVER LIVER NEOPLASMS MUTAGENS QUINOLINES TIME FACTORS TUMOR CELLS, CULTURED