[CD59 mutation and DNA oxidative damage in A(L) cells induced by crocidolite fibers].
OBJECTIVE
To determine the effects of buthionine sulfoximine (BSO) and free radical scavenger, dimethyl sulfoxide (DMSO), on mutation frequency and the formation of 8-hydroxydeoxyganosine (8-OHdG) induced by crocidolite fibers in human-hamster hybrid (A(L)) cells.


METHODS
The cytotoxicity and mutagenicity were determined by the formation of colonies. 8-OHdG was examined by immunoperoxidase staining. Non-protein sulfhydryl (NPSH) compound was assayed by modified Tietze's method.


RESULTS
The level of NPSH in A(L) cell pretreated with 25 micro mol/L of BSO was decreased to 2 nmol/10(7) cells, only 5% of the control after 24 h. The mutation frequency of CD59 gene of A(L) cell in crocidolite alone treated group was 208 +/- 18 while that in BSO pretreated group (397 +/- 55) was about twice the former (P < 0.05). The mutation frequency of CD59 gene in the group treated with crocidolite and in the presence of DMSO (57 +/- 8) was 72.6% less than that in crocidolite alone treated group. Crocidolite fibers induced a dose-effect relationship in the formation of 8-OHdG in A(L) cells (y = 150 + 20x, r = 0.9621). The level of 8-OHdG in cells was 289 +/- 6 at the dose of 6 micro g/cm(2) crocidolite, which was about twice the control group (137 +/- 9). In the presence of DMSO, 8-OHdG level decreased to 170 +/- 3 at the same dose of crocidolite.


CONCLUSIONS
Free radicals are the important inducer of mutagenesis and DNA damage in A(L) cells caused by crocidolite, which has dose-effect relationship.
Xu
An
A
Key Laboratory of Ion Beam Bioengineering of Institute of Plasma Physics, Chinese Academic of Sciences, Hefei 230031, China.
Wu
Li-jun
LJ
Tk
Hei
H
Yu
Zeng-liang
ZL
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017638:Asbestos, Crocidolite / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D018957:CD59 Antigens / Q000235:genetics*; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells; D007124:Immunoenzyme Techniques; D009154:Mutation
D018957:CD59 Antigens; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017638:Asbestos, Crocidolite; D019328:Buthionine Sulfoximine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D004121:Dimethyl Sulfoxide