TY - JOUR
T1 - Inhibition of O6-alkylguanine-DNA-alkyltransferase by metals
AU - Scicchitano, David A.
AU - Pegg, Anthony
N1 - Funding Information:
This researchwas supportedb y NIH Grant CA-18137.
PY - 1987/11
Y1 - 1987/11
N2 - The activity of the DNA-repair protein O6-alkylguanine-DNA-alkyltransferase was found to be strongly inhibited by a number of metal ions. Cd2+ was the most active followed by Cu2+, Hg2+, Zn2+ and Ag2. This inhibition is likely to result from the interaction of the metals with the cysteine-acceptor residue on the protein since the inhibition was reduced by increasing the concentration of dithiothreitol in the assay buffer. These results raise the possibility that exposure to Cd2+ could increase the mutagenicity and carcinogenicity of alkylating agents by retarding the rate of repair of alkylated DNA. However, other metals or metallic compounds which are known to be carcinogenic (such as compounds containing arsenic, lead, nickel or chromium) did not interfere with DNA repair by this protein.
AB - The activity of the DNA-repair protein O6-alkylguanine-DNA-alkyltransferase was found to be strongly inhibited by a number of metal ions. Cd2+ was the most active followed by Cu2+, Hg2+, Zn2+ and Ag2. This inhibition is likely to result from the interaction of the metals with the cysteine-acceptor residue on the protein since the inhibition was reduced by increasing the concentration of dithiothreitol in the assay buffer. These results raise the possibility that exposure to Cd2+ could increase the mutagenicity and carcinogenicity of alkylating agents by retarding the rate of repair of alkylated DNA. However, other metals or metallic compounds which are known to be carcinogenic (such as compounds containing arsenic, lead, nickel or chromium) did not interfere with DNA repair by this protein.
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U2 - 10.1016/0165-7992(87)90057-1
DO - 10.1016/0165-7992(87)90057-1
M3 - Article
C2 - 3683440
AN - SCOPUS:0023525767
SN - 0165-7992
VL - 192
SP - 207
EP - 210
JO - Mutation Research Letters
JF - Mutation Research Letters
IS - 3
ER -