SnCl(2)-induced DNA damage and repair inhibition of MMS-caused lesions in V79 Chinese hamster fibroblasts.
In order to clarify the molecular mechanisms of Sn(2+) genotoxicity, we evaluated the induction of strand breaks, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (Endo III) sensitive sites, and the interference with the repair of methyl methane sulfonate (MMS)-caused DNA damage in V79 Chinese hamster lung fibroblasts exposed to stannous chloride by comet assay. A concentration-related increase in the DNA damage induced by 2 h SnCl(2) treatment at a concentration range of 50-1,000 microM was observed (r = 0.993; P < 0.01). Significantly elevated DNA migration in relation to the control level was detected at doses 100, 500 and 1,000 microM in normal alkaline and at doses 500 and 1,000 microM in modified (with Fpg and Endo III) comet assay. Although 50 microM SnCl(2) concentration did not increase significantly the DNA migration by itself in comet assay, it was capable to inhibit the repair of MMS-induced DNA damage during the post-treatment period of 24 h. Our results demonstrate the genotoxic and comutagenic effects of stannous chloride in V79 cells. The inhibitory effect of Sn(2+) on repair of MMS-induced DNA damage suggests that this metal can also interfere in DNA repair systems thus contributing to increased mutation by shifting the balance from error-free to error-prone repair processes.
Viau
C M
CM
Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, Brazil.
Guecheva
Temenouga N
TN
Sousa
F G
FG
Pungartnik
C
C
Brendel
M
M
Saffi
J
J
Henriques
João Antonio Pêgas
JA
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D053960:DNA Breaks / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D005347:Fibroblasts; D019216:Metals, Heavy / Q000633:toxicity*; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D017971:Tin Compounds / Q000633:toxicity*
D019216:Metals, Heavy; D009153:Mutagens; D017971:Tin Compounds; C023599:stannous chloride; D008741:Methyl Methanesulfonate