Reevaluation of the effect of ellagic acid on N-methyl-N-nitrosourea DNA alkylation and mutagenicity.
N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N7, guanine O6, and adenine N3. Dixit and Gold [(1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8039-8043] reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU in Salmonella typhimurium strain TA 100, inhibited salmon sperm DNA alkylation by [3H]MNU, and also greatly reduced the ratio of guanine O6 to guanine N7 alkylation. We have examined the MNU-induced alkylation of calf thymus DNA and evaluated the effect of ellagic acid on this binding. Ellagic acid had only a slight effect on total alkylation and did not alter the ratio of methylation at guanine-O6 and -N7 positions. In further experiments, ellagic acid did not significantly inhibit MNU mutagenicity. These findings do not support the potential use of ellagic acid as an inhibitor of biological damage induced by nitrosoureas.
Lord
H L
HL
Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry, University of Guelph, Ontario, Canada.
Josephy
P D
PD
Snieckus
V A
VA
D000478:Alkylation; D004247:DNA / Q000378:metabolism*; D004610:Ellagic Acid / Q000494:pharmacology*; D007700:Kinetics; D008770:Methylnitrosourea / Q000378:metabolism* / Q000633:toxicity; D009152:Mutagenicity Tests
D004610:Ellagic Acid; D008770:Methylnitrosourea; D004247:DNA