Nickel chloride inhibits the DNA repair of UV-treated but not methyl methanesulfonate-treated Chinese hamster ovary cells.
Nickel, a human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity, and sister-chromatid exchanges (SCE) induced by ultraviolet (UV) light but not by methyl methanesulfonate (MMS). To verify that the cocytotoxicity and cogenotoxicity of nickel are correlated with its inhibition on DNA repair, the effects of nickel on the DNA repair induced by UV and by MMS have been investigated. Our analyses of DNA repair of single-strand breaks by alkaline elution and alkaline sucrose sedimentation indicate that nickel inhibited the DNA repair in UV-treated, but not in MMS-treated cells. Therefore, the inhibition of DNA repair seems to play an important role in the cocytotoxicity and comutagenicity of nickel. However, the inhibition of DNA repair seems not to play a decisive role in enhancing SCE, because we have previously shown that arsenite inhibits the UV-induced DNA repair, but has no enhancing effect on the UV-induced SCE. Our results also show that nickel had obvious inhibitory effects on DNA ligation and postreplication repair, but had no apparent effect on nucleotide excision and DNA polymerization in the UV repair. The results of the DNA ligation inhibition by nickel in UV but not in MMS repair suggest that different ligases are used in the DNA repair of UV- and MMS-induced damages.
Lee-Chen
S F
SF
Institute of Zoology, Academia Sinica, Taipei, Republic of China.
Wang
M C
MC
Yu
C T
CT
Wu
D R
DR
Jan
K Y
KY
D000818:Animals; D016466:CHO Cells; D002273:Carcinogens / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002499:Centrifugation, Density Gradient; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D006918:Hydroxyurea / Q000494:pharmacology; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity*; D014466:Ultraviolet Rays
D002273:Carcinogens; D003561:Cytarabine; C022838:nickel chloride; D009532:Nickel; D004247:DNA; D008741:Methyl Methanesulfonate; D006918:Hydroxyurea