Reevaluation of the effect of ellagic acid on N-methyl-N-nitrosourea DNA alkylation and mutagenicity

Journal Article · · Chemical Research in Toxicology; (USA)

DOI:https://doi.org/10.1021/tx00015a002· OSTI ID:6363422

Lord, H L; Josephy, P D ^[1]; Snieckus, V A ^[2]

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1. Univ. of Guelph, Ontario (Canada)
2. Univ. of Waterloo, Ontario (Canada)

N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N{sup 7}, guanine O{sup 6}, and adenine N{sup 3}. 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 ({sup 3}H)MNU, and also greatly reduced the ratio of guanine O{sup 6} to guanine N{sup 7} 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-O{sup 6} and -N{sup 7} 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.

• OSTI ID: 6363422
• Journal Information: Chemical Research in Toxicology; (USA), Journal Name: Chemical Research in Toxicology; (USA) Vol. 3:3; ISSN CRTOE; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATION
AMIDES
AROMATICS
CARBONIC ACID DERIVATIVES
CHEMICAL REACTIONS
CHROMATOGRAPHY
DNA
HYDROXY COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MEASURING METHODS
MUTAGENESIS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOLS
SEPARATION PROCESSES
UREA