Reactivity of fecapentaene-12 toward thiols, DNA, and these constituents in human fibroblasts.
Cancer Res
; 49(21): 6058-63, 1989 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-2790820
Micromolar concentrations of fecapentaene-12, a mutagen found in human feces, decrease survival measured as colony-forming efficiency and membrane integrity of cultured human fibroblasts. Fecapentaene-12 also decreases the content of cellular free low-molecular-weight thiols including glutathione. Fecapentaene-12 reacts directly with glutathione by causing both decreased levels of free thiol and some concomitant formation of oxidized glutathione, indicating that thiol depletion is a result of both alkylation and oxidative reactions. Exposure of cells to 2 or 5 microM fecapentaene-12 causes significant amounts of DNA-interstrand cross-links and DNA-single strand breaks, respectively, whereas exposure to a higher concentration of fecapentaene-12, i.e., 10 microM, also causes significant DNA-protein cross-links. Results from the reaction of fecapentaene-12 with isolated plasmid DNA parallel the cellular pattern of DNA damage; primarily interstrand cross-links and strand breaks occur also in plasmid DNA. Taken together, these studies show that fecapentaene-12 is a potent cytotoxic and genotoxic agent which can react with cellular thiols and cause several types of DNA damage.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polienos
/
Pele
/
Dano ao DNA
/
Glutationa
/
Mutagênicos
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1989
Tipo de documento:
Article