Role of oxyradicals in mutagenicity and DNA damage induced by crocidolite asbestos in mammalian cells.
Cancer Res
; 59(23): 5922-6, 1999 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-10606236
ABSTRACT
Crocidolite, one of the most carcinogenic forms of asbestos, is mutagenic in cultured mammalian cells when assayed using a system that can detect multilocus deletions. In the present study, we examined the effect of buthionine sulfoximine (BSO) on mutation frequency and the formation of 8-hydroxydeoxyguanosine (8-OHdG) in human-hamster hybrid (A(L)) cells induced by crocidolite fibers in an attempt to determine the role of oxyradicals in mediating fiber mutagenesis. BSO, a competitive inhibitor of the enzyme gamma-glutamyl cysteine synthetase, depleted nonprotein sulfhydryls to <5% of control within 24 h at a nonmutagenic dose of 25 microM. In cells pretreated with BSO for 24 h, the mutation yield at the CD59 locus induced by a 4 microg/cm2 dose of crocidolite fibers was increased by more than 3-fold (P < 0.05). Using immunoperoxidase staining with a monoclonal antibody specific for 8-OHdG, we demonstrated that crocidolite fibers induced a dose-dependent increase in oxidative DNA damage in A(L) cells. Furthermore, addition of DMSO, a well-established hydroxyl radical (OH*) scavenger, dramatically suppressed 8-OHdG induction (P < 0.005). Our results definitely demonstrate that reactive oxygen species mediate fiber-induced DNA damage mutagenesis in A(L) cells in a concentration-dependent manner.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Amianto
/
Dano ao DNA
/
Asbesto Crocidolita
/
Butionina Sulfoximina
/
Desoxiguanosina
/
Mutagênicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos